How do we know if there is any residual clonazpeam in the jar after consuming it

[[Buddie]]

We switched over to liquid titration for my wife's taper off the final 0.25mg. We liquified it in a mason jar and shook it around.  We then put more water in there, shook it again and drank it.. and a third time for good measure. 

Would that get all of the remaining particles?  We noticed some particles in the center before she first drank it and just want to make sure she gets the entire % of her titrated amount.

[[Buddie]]

Tip of the hat for recognizing that drug loss due to surface transfer is a known issue when modifying commercially available drug products to use in do-it-yourself (DIY) preparations.

Rinsing surface(s) that come into contact with the modified drug form and consuming the rinse water has been found to decrease drug loss/improve drug recovery. For example, in the first study linked below, rinsing the crushed powder from a tablet crusher with water once resulted in an average of 24.2% drug loss; this was reduced to 4.2% after a second rinse. In the second study, the mean range of recovery of crushed oral doses after rinsing with 100mL of water twice and stirring repeatedly was 98-100%. 

Fyi … we do not know the properties of DIY liquids because, to our knowledge, none of them has been professionally analyzed.  Our current thinking is that DIY liquids such as the one you are making are probably suspensions, not solutions.  If so, there is no guarantee that each and every milliliter of the liquid contains exactly the same amount of drug. Strategies used by members to address this include ensuring that drug/excipient particles are as uniform in size/shape as possible and shaking the liquid well before quickly measuring the desired dose/reduction amount.

I hope your wife was able to transition from solid dosage form to DIY liquid without issues!

Links:
Drug loss while crushing tablets: Comparison of 24 tablet crushing devices
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193683

Evaluation of Crushed Ticagrelor Tablet Doses: Recovery Following Crushing and Naso-gastric Tube Passage Ex Vivo
https://link.springer.com/article/10.1007/s40268-013-0018-4

[[Buddie]]

Thank you for that description. that was very helpful.

[[Buddie]]

You are most welcome.  Your steadfast support of your wife is admirable.

If I’m understanding your wife’s progress log correctly, you are now using the ‘reduce by 1mL a day’ approach starting with 90mL of DIY liquid.  If so, please be mindful that one of the ‘gotchas’ of the fixed- amount reduction approach is that the percent reductions increase over time, sometimes to levels the individual cannot tolerate. For example, decreasing the amount of liquid consumed from 90 to 60mL over the first 30 days of the taper would be a 33.33% reduction in dose.  Decreasing the amount of liquid consumed from 60mL to 30mL over the second 30 days of the taper would be a 50% reduction in dose.

[[Buddie]]

Thank you for that advice and your kind words. They are encouraging in light of the constant negativity and anger I hear from my wife as she goes through this horrible ordeal which I can see is very difficult.  I'm hoping she realizes how helpful I've been once she's off of this medication and becomes a bit more positive.

Your point is something I'm concerned with and wondering if sticking to the neurologist's tapering strategy may be better suited for her.  I think (don't know) that the manner in which he helped her taper gave her these 2-day windows of feeling generally good, whereas the constant daily microtapering can cause her to feel the same throughout the 30 days without any stabilization.  Would that be accurate?  Her first two days on this method have been a bit rough on her. She's been more emotional than usual and had less sleep. We are hoping this is just her getting used to consuming the clonazepam in a suspension as opposed to consuming a pill that then absorbs in her stomach more slowly and that she can take to it.  We were told to go to the liquid taper because the prior plan puts her at risk of kindling.

[[Buddie]]

I’m delighted to learn that my words gave you some measure of encouragement. I know how discouraging and dispiriting benzodiazepine discontinuation can be for both the person experiencing it as well as those who love them.  I also am certain that your wife recognizes and is deeply grateful for your help and support.  She is just too over-whelmed by her withdrawal symptoms to express this to you at this time.

I am not a pharmacologist but my understanding is the tapering strategy proposed by the neurologist is problematic because it causes drug serum levels to fluctuate more widely than taking the same amount of drug each day.  My further understanding is that consistency in serum levels (i.e. keeping levels as steady as possible) is preferred during discontinuation. (At this time, I personally am unaware of any credible clinical or experimental evidence to support the claim that the neurologist’s strategy increases the risk of kindling.)

I’m sorry your wife is experiencing an uptick in symptoms after switching to the DIY liquid.  Some members have issues with liquids whereas others do not.  Options to consider include (1) return to the starting dose of 0.25mg and hold at that dose for a week or so in hope that symptoms will settle down, (2) titrate the dose upwards slightly to see if that helps, (3) use a combination of solid and liquid dosage forms (e.g. a 0.125mg orally disintegrating tablet plus 0.125mg in liquid form, reduce the liquid portion to 0.0mg then taper the remaining 0.125mg in liquid form), and (4) trial a different liquid (e.g. a professionally compounded oral suspension or a DIY milk-based liquid).

I’ll close by sharing a common misconception — that is, the only way to ‘microtaper’ (i.e. make ‘small enough’ reductions in dose) is on a daily basis.  This is not the case.  We have members who make small reductions every other day, every third day, every week, every other week, etc.  We also have members who make a series of small daily reductions followed by a hold.  (When using a fixed-amount reduction strategy, adjusting the taper interval allows the individual to keep the overall taper rate within a tolerable range.)

[[Buddie]]

Thank you for the kind words, the support, and the clearest, most intelligent explanation I’ve heard on this topic. I really appreciate you this and will be using this advice to help my wife.

[[Buddie]]

I’m glad I could help.  Please do keep us posted.  I’m sending all good thoughts and best wishes your way for a positive outcome!

[[Buddie]]

Thank you. Today we took a step back and brought her back to 0.25mg in the diy titration, just to validate whether or not she takes well to it as opposed to just taking the pill.  If she's good then we'll carry on, otherwise we'll move to dry taper once more.

[[Buddie]]

Hello, [...].

I came across an article and graphic today I thought you might find of interest:

Peaks and Troughs: What Are They, and More
https://www.osmosis.org/answers/peaks-and-troughs

As shown in the graphic, taking a consistent amount of drug at a consistent time (or times) each day results in a consistent (steady state) peak and trough pattern. Taking a different amount of drug each day (as suggested by the neurologist) disrupts this pattern.