Alternative liquid tapering idea (Just a thought..)

[[Ph...]]

This is something I've been thinking about for a while, and would mostly apply to those who are tapering with ativan or xanax (shorter half lives). So what if instead of doing traditional dry cuts or liquid tapers divided up into however many doses, you were to essentially 'drink' your dose throughout the day. This could potentially prevent some of the interdose WD especially associated with these shorter half life meds. Hear me out..

 

Example: Patient is taking 0.5mg xanax twice daily, once in the morning and once in the evening. They could take their 0.5mg in the evening before bed, but instead of taking the whole 0.5mg in the morning, it could be crushed up, put into a liter of water, and the individual could slowly drink it through the day. Of course if it was just water, it would need to be constantly shaken, but if mixed in with another solvent such as propylene glycol or alcohol that are often used in other liquid tapering methods, this would not be an issue. I'm not sure how palatable this would be, but it might be dilute enough to not have much of a bitter taste. And if that were a problem, I'm sure there are many flavoring agents that could be used to make it more palatable.

 

This would certainly provide the most even levels throughout the day (almost like an IV drip), and would seemingly provide the smoothest transition when titrating downward. I probably am not the first to have thought of, or to have mentioned this, but there is months worth of reading on these boards! Anyway, just a thought..

[[fi...]]

Hi pharmguy!!  Guess what?!? Magnesia is doing just that with a compounding pharmacies and I asked her for details re suspension vehicle concentrations calculations etc etc -when it's done.  I'lll ask her to post the details here since if we're both interested maybe others are too, or could benefit as well ! 

[[ne...]]

Hi Pharmguy, interesting idea, but I'm thinking that taking the benzo throughout the day it will mean that only a tiny dose will be taken at any one time. So wouldn't that tiny dose be then metabolized out of your blood by the liver before it reaches a therapeutic/effective level in the brain?

[[ma...]]

Hello Pharmguy,

 

All I know about these meds is what I had to learn to get rid of Ativan, but it seems a valid idea. Some  antidepressants are "extended release". They use special gel capsules or additives, so that the active compound is released slowly. But, indeed, I don't know of any benzo that works like this.

 

What I'll be doing is a normal liquid tapering but with a suspension prepared at the pharmacy. It'll be a 1mg to 10ml suspension using as a vehicle a product called SyrSpend® SF. I'm waiting for the suspension to be ready since last week. It seems to be a very unusual request here!

 

All the best 

[[Ph...]]

Firefly1, New0girl, and Magnesi.. thanks for your replies.

 

Magnesi, I'm glad to hear that you've found a compounding pharmacy to work with you on your taper. I'm assuming your are sticking with ativan (as opposed to a valium crossover)? SyrSpend is a good and commonly used suspending agent. The only difference in using a suspending agent, as opposed to a solvent like polyethylene or propylene glycol, is that the suspending agent 'suspends' the drug in the formula so that it is evenly distributed (as opposed to sinking to the bottom like it would in water), whereas a solvent would essentially dissolve the drug in the solution. Either way, both serve the same purpose.. even distribution throughout the vehicle.

 

I almost forgot about this, but there are some benzos and z-drugs that do have some sort of extended release formulation. For example, there is ambien CR. In this case there is a bi-phasic release, so it's kind of like you take one pill before bed where the first half kick in, and then the other half kicks in 4 hours later. There is also Xanax extended release. It's model is based on a slower absorption into the bloodstream, and apparently has a completely EVEN plasma concentration between hours 5-11 (had to look this up).

 

Just a side note, there are several premade liquid formulations that would be ideal for us to taper with (as opposed to doing all of the measurements and weighing ourselves), but you don't see them often. The only time I ever saw them is when working for a pharmacy that provided meds to nursing home facilities where many of the patients could not swallow whole pills. I doubt many retail pharmacies would carry these, but they could always be special ordered if the doc would be willing to prescribe. I have only seen the ativan liquid formulation personally, but know there is one for diazepam as well. My biggest concern with this, is that they might be much more expensive than the pills, and not sure if insurance would cover. When working at that pharmacy, we did not have to deal with the insurance side of things, so I can't say for sure.

 

New0girl, that's actually a very good question! And a highly complex one as well. There are so many variables that effect how long a drug remains in our system and on our receptors (genetic factors which affect rate of metabolism, liver and kidney function, ect). So the answer is not really a yes or a no. Just using the example of the extended release xanax mentioned above (which in terms of absorption, would be similar to slowly drinking a liter of xanax water throughout the day), I'd say that the issue you proposed would not be a problem. To start with, even if we take a dose every 12 hours, there is still some left in our system right before our 2nd dose (say at 11 hours and 59 minutes). It then becomes the difference of taking one large dose that floods into the bloodstream and onto the receptors all at once where the drug is thereby slowly knocked off of the receptors, and eliminated from the bloodstream, as opposed to taking lots of little doses throughout the day which are constantly doing the same thing. The half life of the drug in this case isn't going to change based on how much or how little of it is taken, or when it is taken. It is almost like bringing in a whole army or rescue workers in all at the same time to fix some particular problem, as opposed to bringing in a few at a time while the others are beginning to leave (maybe not the best analogy, but the best I could think of ) This could present other problems, however. Some may NEED (due to anxiety for example) that immediate relief in the morning (or whenever their dose is) whereby they receive the entire dose at once. But either way, the "average" levels in your bloodstream over a given period are going to remain the same (and actually at a much more even level than they would had the dose been given all at once or twice daily). Below is a graph to illustrate that point..

 

 

You can see here that the even middle straight line is a continuous infusion, showing even levels in the bloodstream. The other two are based on intermittent dosing (say twice daily). The total dose given within a 24 hour period IS the same, and the AVERAGE levels in the bloodstream are also the same, but you can see that there are some serious peaks and valleys with intermittent dosing, whereas there are none with continuous infusion (ie. drinking the water slowly throughout the day). The following shown below is an even more extreme example (look at the top illustration) of a drug that has a very short half life (ie xanax). That's what your plasma levels might look like if dosing only once daily (huge peaks and valleys)

 

 

HOWEVER, the biggest problem or question with all of this is not necessarily the levels that can be measured in the bloodstream, but how long the benzo molecules stay attached to the receptors, and how a continuous infusion type of dosing might affect this. We can't actually presume to know any of this with certainty because this is something that is much harder to measure. How would the effect of small amounts of a drug hitting the receptors gradually throughout the day differ, or affect WD or alter the drugs effect, as opposed to getting a larger dose all at once. I'm not 100% certain, but I believe that if you reach a point of steady state (the amount of drug entering the body iss equal to the amount of drug leaving the body over a given period), than "I" personally do not believe it should cause a problem.

 

Finally, the last thing that comes to mind is whether having a consistent level in both our bloodstream and on our receptors IS actually the best method of slowly tapering. OR, dose some amount of interdose WD actually begin the healing process? I can't say for sure. This is all speculation, and we are still in somewhat uncharted territory here.

 

If I personally were tapering off a 1mg daily dose of xanax, and wanted to try this, in order to provide for the smoothest transition, I might try taking 0.25mg in the AM, mixing 0.5mg in my liter of water/solvent and drinking throughout the day, and then taking 0.25mg at night. I might try it this way in order to avoid disrupting whatever rhythm I had previously had with my other dosing schedule.

 

Someone is going to need to be a guinea pig here To be honest, even though I am currently using valium, I might give this a try.. if for no other reason then the fact that I HATE waking up and taking a dose of valium. Trying to wake up, only to be further sedated is not appealing to me. But even with valium I've found that dosing several times throughout the day seems to provide more benefit than waiting until the evening and taking it all at once.

 

Anyway, remember that this is just all food for thought. Feedback is welcome..

 

[[fi...]]

Wow Pharmguy..I feel like i'm back in school!!! Graphs and all!!! lol ....in a good way!!!

did you ever teach?!?

YOU SHOULD!!!

and as i was reading and in my head about to ask certain questions..there you were...asking the same questions...with the same unknowns etc.. following the same thinking (i love that style of teaching!!)

 

wow..you should teach!

 

and i didn't realize you were on valium right now (benzo brain)...

i am debating if i might have to go that route (as i have only started to stabilize on zopiclone/ativan  and not yet taper the ativan but feeling it - or lack thereof - in the hours before my evening dose) - but i am loathe to do that because i like having my wits about me in the day - best part of my day is when the ativan starts to wear off and my head clears up...of course..then comes the evening and i start feeling the LACK of ativan.  truth is - i'm not even sure if i might not be feeling a lack of it in the day - but tolerable now...not sure it will be as i start to taper ...

 

trying to arm myself with all possible options beforehand - and to talk to whomever i might need to BEFORE things get problematic

 

thank you to both of you...ALL of you!!

so helpful !!

 

but i'm scared if i cross over to valium i'll have my head feeling like cotton balls all day (that's what i read online people say it's like)

 

you know what i'm talking about? having your wits about you?

 

can you elaborate - just a little - about why you find it better to space out the dose - it is after all a long acting drug.

just quells the withdrawals better??? is that it?

[Guest [ba...]]

Nice to see somebody else doing 1st order kinetics. 

[[ma...]]

Magnesi, I'm glad to hear that you've found a compounding pharmacy to work with you on your taper. I'm assuming your are sticking with ativan (as opposed to a valium crossover)? SyrSpend is a good and commonly used suspending agent.

 

Hi Pharmguy,

Yes, I'm not thinking of doing a valium crossover as I'm not having many interdose withdrawal symptoms. I'll try to just taper off Ativan. Good to know about SyrSpend . It's neither very cheap nor covered by insurances or the public system here, but I'm hoping to not stay with it for very long and, well, health is important.

 

I'll comment on the rest of your post tomorrow, I would like to read it again 

[[Ph...]]

Nice to see somebody else doing 1st order kinetics. 

 

[[Ph...]]

Wow Pharmguy..I feel like i'm back in school!!! Graphs and all!!! lol ....in a good way!!!

did you ever teach?!?

YOU SHOULD!!!

and as i was reading and in my head about to ask certain questions..there you were...asking the same questions...with the same unknowns etc.. following the same thinking (i love that style of teaching!!)

 

wow..you should teach!

 

and i didn't realize you were on valium right now (benzo brain)...

i am debating if i might have to go that route (as i have only started to stabilize on zopiclone/ativan  and not yet taper the ativan but feeling it - or lack thereof - in the hours before my evening dose) - but i am loathe to do that because i like having my wits about me in the day - best part of my day is when the ativan starts to wear off and my head clears up...of course..then comes the evening and i start feeling the LACK of ativan.  truth is - i'm not even sure if i might not be feeling a lack of it in the day - but tolerable now...not sure it will be as i start to taper ...

 

trying to arm myself with all possible options beforehand - and to talk to whomever i might need to BEFORE things get problematic

 

thank you to both of you...ALL of you!!

so helpful !!

 

but i'm scared if i cross over to valium i'll have my head feeling like cotton balls all day (that's what i read online people say it's like)

 

you know what i'm talking about? having your wits about you?

 

can you elaborate - just a little - about why you find it better to space out the dose - it is after all a long acting drug.

just quells the withdrawals better??? is that it?

 

Haha, no I've never taught. Maybe one day..

 

Yes, I'm on valium. I was previously on several different benzos, but for the most part it was klonopin and valium, both longer acting, so the decision was easy. As for why I still take it multiple times throughout the day.. well I don't have any genetic test results to confirm this, but I believe that I am likely a rapid metabolizer as the effects of valium don't seem to affect me near as long as they should. I'm still trying to find stabilization after reinstatement, and have just noticed that if I cut and spread the doses throughout the day, I experience less symptoms between doses (anxiety, muscle tightness and a feeling of heaviness, occasional racing thoughts).

 

Anyway, as far as you considering switching to valium goes, I know that's a tough decision. If you are actually doing relatively 'ok', I might consider trying a taper with ativan first since your body is used to it. A lot of people have problems doing a crossover. This is not advice per se, but just what I'd probably thinking if I were in your position.

 

And yes.. I absolutely know what you mean about not looking forward to taking it in the morning, and how the best part of the day is when it starts wearing off, but before the anxiety/WD starts to kick in. There is certainly a sweet spot to be found in there somewhere. Best of luck to you in whatever your decision happens to be

[[Ph...]]

Magnesi, I'm glad to hear that you've found a compounding pharmacy to work with you on your taper. I'm assuming your are sticking with ativan (as opposed to a valium crossover)? SyrSpend is a good and commonly used suspending agent.

 

Hi Pharmguy,

Yes, I'm not thinking of doing a valium crossover as I'm not having many interdose withdrawal symptoms. I'll try to just taper off Ativan. Good to know about SyrSpend . It's neither very cheap nor covered by insurances or the public system here, but I'm hoping to not stay with it for very long and, well, health is important.

 

I'll comment on the rest of your post tomorrow, I would like to read it again 

 

Magnesi, sorry to hear that this might end up being a bit expensive for you due to lack of insurance coverage. I'm having to pay out of pocket for a lot of this stuff as well . Fortunately you've at least found a doctor willing to work with you on your taper Based on your sig, it seems you are doing pretty well, and so I certainly don't blame you for not attempting to cross over to valium. Hope everything goes well!

[[fi...]]

PharmGuy

...accidental delete when meant to edit..oh well..

oh well..

it'll come back around

[[ne...]]

Hello PharmGuy, it's wonderful to have a pharmacist here that can explain things so clearly! You are an asset to this forum. 

 

It was very captivating to read your explanation, but I still have one questin, please bear with me here. From what I know, 'continous infusion' means the administration of a fluid into a blood vessel through an IV port, so it's not exactly the same thing as drinking a diluted drug over many hours. Is there a difference betwen the dose of a drug that undergoes intestinal absorbion versus direct blood administration? I mean besides the fact that the latter reaches the brain faster. Are there any "loses" in potency through GI absorbion?

 

Firefly, good luck with your planning, I remember when I was in your position two months ago. It's sooo difficult to take a decision with all these unknowns. Sometimes we just got to close our eyes and jump with no safety net... 

 

I'm sending my good wishes to anyone who might be reading. Take care, everyone!

xoxo

 

[Guest [ba...]]

Since a person would want to sleep at night, a boost dose would be required in the morning.  This simulation shows the drug level over time assuming hourly dosing, except from midnight thru 6 am (inclusive).  The boost dose is just over 6x the hourly dose.  Half life is 10 hours.

 

http://enchantedskies.net/ContinuousAtivan.jpg

 

As for oral versus IV - I would assume that first pass metabolism is fairly linear, but pharmguy would know more about this.  I'm sure there would be some variation due to food intake, water intake...

[[ne...]]

Bads, you have some interesting hobbies. 

xoxo

[Guest [ba...]]

Bads, you have some interesting hobbies. 

xoxo

 

If you only knew... 

[[ne...]]

:laugh: Hahahaha

 

NOW I'm scared!

[[Ph...]]

Firefly, sorry you lost your post. I believe I read some of it right before falling asleep, and I recall you (I think?) saying something about diazepam making some feel like they have cotton brain. Hmm.. I've taken several different benzos, and although they are all different, they all (at least to me) seem to have that same 'benzo' effect, which does feel a bit like cotton brain. It might be that this particular effect is more pronounced with diazepam. I can say for me that it is a bit less 'relaxing' than klonopin, and especially xanax. Whereas I'd agree that klonopin does seem to have slightly more of a depressant effect that some people complain about. BUT.. we are all so unique in how these drugs effect us.

 

Badsocref, Great chart!  I guess this is probably a slightly more accurate representation of what doing something like I had suggested earlier in this thread might look like on a chart (since we obviously can't live our lives hooked up to an IV or drinking water in our sleep ) Just upon visual inspection, it does look like a fairly large drop off at 'bed time', but looking at the actual numbers, it seems to show a concentration range of about 0.85 to 0.55, which really isn't that bad, especially compared to what you might see with something like 2-3 times daily dosing of a short acting benzo.

 

New0girl, another great question! I wan't to clarify a couple of things. My original chart example was just an estimation using a continuous infusion as an example, and as badsocref pointed out with his chart, there would still be fluctuations overnight. In fact, there are very few benzos that are EVER given IV, although you will see ativan and diazepam given IM, especially in hospitals and nursing homes. The KEY thing here to understand is oral bioavalibility. And the oral bioavalibility of most benzos is usually 90% or more. This just means that 90% of the dose taken orally will find it's way into the bloodstream (although it might take a bit longer). So for all intents and purposes, the chart I proposed would hold true. Of course it is just an estimation, and there would be minor differences due to rate of absorption being slower for some, and other factors like food slowing down the absorption into the bloodstream. So in reality, that line on the first graph would not be quite as even, but would probably have a few little bumps and drops here and there (not to mention the fact that it would be difficult to drink a liter of water at such a constant as to mimic a calculated continuous infusion). Also, the line would be approximately 10% lower due to most benzos being 90% orally bioavailable. But none of us were IVing this stuff anyway. So besides the few small bumps due to absorption issues, as well as the overnight dropoff, Id say that the answer is no.. there would not be much of a difference. Just a potential idea to get levels as close as possible to remaining at a consistent concentration without hooking ourselves up to an IV  . And thank you for the kind words and well wishes! All the best to you as well

[[Su...]]

Hi Pharmguy and all,

There is a very detailed explanation with research to explain the physical mechanics in the Chewing the Fat section under the thread :

"Can someone explain this to a layperson"

I know this is your field Pharmguy, and the papers explain that it is very helpful to have a consistent amount of med in the body, that the peaks and valleys actually are detrimental to healing, the reason that switching over to a longer half-life med can be helpful.

 

So your theory and the idea makes lots of sense Pharmguy 

I know that even though I take Valium 4X a day, there are times when I need to nibble on a dose before the time I usually dose.  This keeps sxs to a minimum and, if the research is correct, helps the healing.  There seems to be a big difference between the half-life of Valium and the duration of action.  I actually find that Xanax has a longer duration of action for this body.... I have no problem going 12 hours between my bed-time dose and my dose of Valium 12 hours later.... 

 

FF, I switched over a bit of my Xanax dose to Valium and that has helped with interdose w/d but has brought some issues with it.  In retrospect I wish I had stayed with Xanax alone, or had only allowed myself to take at the most 2mg of Valium. It has brought with it huge fatigue, low mood,  and doesn't feel as "clean" a med as Xanax if that makes sense to anyone.  It's a strange medication, at least for me, and I knew what Xanax did with this body -- I'd been on it for so long  .  Funny, not funny....  My doc suggested the Valium but has left the dosing up to me.  Just telling you my experience as you make your own decision about it all....

 

Thanks for starting the thread Pharmguy.

SS

 

[[fi...]]

Thanks SufferingSixty.

 

It helps to hear others' stories like this.

It really does.

 

I don't know what i'll do yet.  And i guess i'll have to see as the taper progresses.

I just don't like that ativan causes ups and downs and that's detrimental - and yet the best part of my day is when my head clears (when it's wearing off) - and yet, soon enough i'll feel w/d shortly before the next dose..catch 22.

 

i don't want to be loopy in the day or feel that cotton brain 24/7 but i want my receptors to heal properly.

it's a catch 22.

i'll figure it out.

 

thanks again for your experiences

firefly

p.s. also that i keep hearing over and over about how valium is depressing to many keeps me thinking i'll stick with what i know (what my body knows) - at least for now. 

[[Su...]]

Hey FF,

Do you have a sig somewhere?

SS

[[Ja...]]

This is a really interesting (and compelling) conversation!

Thank you for posting it!

 

Has anyone tried it yet?

[[Ph...]]

This is a really interesting (and compelling) conversation!

Thank you for posting it!

 

Has anyone tried it yet?

 

Not that I am aware of, but I might end up giving it a shot in the near future..

[[Ph...]]

Hi Pharmguy and all,

There is a very detailed explanation with research to explain the physical mechanics in the Chewing the Fat section under the thread :

"Can someone explain this to a layperson"

I know this is your field Pharmguy, and the papers explain that it is very helpful to have a consistent amount of med in the body, that the peaks and valleys actually are detrimental to healing, the reason that switching over to a longer half-life med can be helpful.

 

So your theory and the idea makes lots of sense Pharmguy 

I know that even though I take Valium 4X a day, there are times when I need to nibble on a dose before the time I usually dose.  This keeps sxs to a minimum and, if the research is correct, helps the healing.  There seems to be a big difference between the half-life of Valium and the duration of action.  I actually find that Xanax has a longer duration of action for this body.... I have no problem going 12 hours between my bed-time dose and my dose of Valium 12 hours later.... 

 

FF, I switched over a bit of my Xanax dose to Valium and that has helped with interdose w/d but has brought some issues with it.  In retrospect I wish I had stayed with Xanax alone, or had only allowed myself to take at the most 2mg of Valium. It has brought with it huge fatigue, low mood,  and doesn't feel as "clean" a med as Xanax if that makes sense to anyone.  It's a strange medication, at least for me, and I knew what Xanax did with this body -- I'd been on it for so long  .  Funny, not funny....  My doc suggested the Valium but has left the dosing up to me.  Just telling you my experience as you make your own decision about it all....

 

Thanks for starting the thread Pharmguy.

SS

 

SS, thanks for the reply. And thank you very much for the link stating that "it is helpful to have a consistent amount of med in the body, that the peaks and valleys actually are detrimental to healing". Although this seemed intuitive to me, I did not have any facts to back it up. So it is nice to have a little more research to back it up.

 

As far as switching over to valium from xanax (or any other med as this applies to anyone), I would not blame someone for at least initially attempting a taper on the med that they are use to. Some have a difficult time with valium, others with klonopin. Sometimes I wonder if I should have just stuck with klonopin since that is what my body had become acclimated to. It's half life is farily long as well, although highly variable.

 

Many also find that they have to dose valium several times per day even with such a long half life, and there are some complicated theories as to why this might be. For some, it might simply be that they are fast metabolizers of valium which is primarily metabolized by CYP3A4. But even so, there could be other factors. Some theorize that valium does not have a very strong binding affinity to it's receptors, so it is displaced rather quickly, leaves the brain and goes back out into the bloodstream. Valium is highly lipophilic so it enters the brain fairly quickly, but also leaves just as quickly. Because it is lipohphilic, it is then widely distrusted throughout the body in fat tissue. Many believe that once it is stored in the fat tissue, it is often metabolized and/or excreted out of the body before entering back into the brain. Also, valium is highly protein bound (over 98% I believe). Drugs that are protein bound in the plasma generally do not exert any effect on their targeted receptors (it is the free/non protein bound portion of the drug that attaches to the receptor), so valium, being protein bound once leaving the blood brain barrier, and then eventually being metabolized and eliminated before re-crossing the blood brain barrier is another proposed theory for why it's duration of action does quite not line up with it's half life. Finally, diazepam actually has 3 active metabolites, all with varying degrees of potency and half lives, so that tends to muddy the waters even more. It is a tricky drug, and I've yet to find anything fully explaining the reason behind it's short duration of action (and especially in some more than others), and it's half life.

[[Su...]]

yep, no wonder it doesn't feel as "clean" as Xanax.  Gets stored in the fat?  Ugh!

The longer I'm on it the more I dislike this med... but it gets me through the days....

SS