Is liquid Valium available in the United States?

Thanks. 

From what pharmacy do you get your "potency- and stability-tested, compounded oral suspension"?

That would save me making the scary switch from K to V.

The compounding pharmacy I use is a small independent that serves a limited area.  Here is the formulation my compounding pharmacist uses:

0.1mg/mL Clonazepam Oral Suspension

https://www.nationwidechildrens.org/-/media/nch/specialties/pharmacy/compounding-formulas/clonazepam-oral.ashx

What do they charge you for the service? 

It seems involved but pretty straightforward.  I just don't understand how they'd get 100% of the mixture out of the mortar.  I guess it wouldn't be right on the dose, but close enough and repeatable.

Do you know of anyone on the board that's doing it themselves?

Thanks again.  After my first taper, I'm scared of all of this.

You just need a mortar and pestle to grind the pills and get the suspension as liberta's directions paper indicates. Very little remains in the mortar. In my case I put just a tinny bit more of a pill and suspending vehicle. Example: if I'm gonna use 10 pills I put 1/4 more of a pill but in realty you don't need to do this, almost nothing is left in the mortar if you do it right. 

I started my taper from 0.750 mg. of clonazepam. I grind 10 pills of 0.5 mg and pour 50 ml of Ora Plus to form a suspension of 1mg/ml. (0.5x10/50). If you have 1 mg pills you use 100 ml of liquid. in this case you need a 100ml bottle.

Because I use liquid and pills and my pills are of 0.5 mg I use a small bottle for just 50 ml of suspension. I reduce 0.005 ml per day combined with the pills so the suspension last for a long time. I try to do a new suspension every month and 1/2. Although you can use all liquid I noticed that the combination of both is more practical.

The big advantage of this is that you use the same type of pills you are taken and also more important not all the compound pharmacies have the same pill size and manufacturer.

Hope this helps.

Mice

Re: minimizing drug loss due to surface transfer …

Thong et al (2018) reported that up to 99.5% of drug (see note below) was recovered by rinsing the crushing device (e.g. mortar and pestle, pill crusher) two times with water.  Interestingly, these researchers also reported that an agate mortar and pestle produced much less drug loss due to surface transfer than a mortar and pestle made of porcelain or glass.

Lee et al. (2005) developed a method to prepare a lorazepam suspension without using a crushing device:

Lorazepam suspension was extemporaneously prepared by a pharmacist/investigator on the morning of the study. One hundred and eighty 2-mg lorazepam tablets were placed in a 12-ounce amber glass bottle and sterile water was added to disperse the tablets. The bottle was vigorously shaken for at least one minute until a slurry was formed. Thereafter, a suspending vehicle, Ora Plus, and a sweetening agent, Ora Sweet were added by geometric dilution to achieve a final suspension volume of 360 mL …. The suspension was shaken and immediately divided into sixteen 2-oz amber glass bottles. Lorazepam suspensions extemporaneously prepared in this fashion were found to be stable.

Note: Please keep in mind that pharmaceutical manufacturing standards allow the amount of Active Pharmaceutical Ingredient (API) in tablets to vary. For example, according to the Indian Pharmacopoeia (Uddin et al, 2015), the API amount can vary by +/- 10% between tablets (i.e. from 90 to 110%).  While this degree of variability is unlikely within a given lot, it is possible between lots.

Citations:

Thong MY, Manrique YJ, Steadman KJ. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices. PLoS One. 2018;13(3). Accessed online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832315/

Lee WM, Lugo RA, Cash J, Rusho WJ, Mackay M, Welkie K. The accuracy and precision of measuring Lorazepam from three liquid preparations. J Pediatr Pharmacol Ther. 2005, 10(1):36-42. Accessed online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468096/pdf/i1551-6776-10-1-36.pdf

Uddin, Md. Sahab et al. In-process and finished products quality control tests for pharmaceutical tablets according to Pharmacopoeias. Journal of Chemical and Pharmaceutical Research. 2015, 7(19): 180-185.  Accessed online at: https://www.jocpr.com/articles/inprocess-and-finished-products-quality-control-tests-for-pharmaceutical-tablets-according-to-pharmacopoeias.pdf

Re: minimizing drug loss due to surface transfer …

 

Thong et al (2018) reported that up to 99.5% of drug (see note below) was recovered by rinsing the crushing device (e.g. mortar and pestle, pill crusher) two times with water.  Interestingly, these researchers also reported that an agate mortar and pestle produced much less drug loss due to surface transfer than a mortar and pestle made of porcelain or glass.

 

Lee et al. developed a method to prepare a lorazepam suspension without using a crushing device:

 

Lorazepam suspension was extemporaneously prepared by a pharmacist/investigator on the morning of the study. One hundred and eighty 2-mg lorazepam tablets were placed in a 12-ounce amber glass bottle and sterile water was added to disperse the tablets. The bottle was vigorously shaken for at least one minute until a slurry was formed. Thereafter, a suspending vehicle, Ora Plus, and a sweetening agent, Ora Sweet were added by geometric dilution to achieve a final suspension volume of 360 mL …. The suspension was shaken and immediately divided into sixteen 2-oz amber glass bottles. Lorazepam suspensions extemporaneously prepared in this fashion were found to be stable.

 

Note: Please keep in mind that pharmaceutical manufacturing standards allow the amount of Active Pharmaceutical Ingredient (API) in tablets to vary. For example, according to the Indian Pharmacopoeia (Uddin et al), the amount can vary by +/- 10% between tablets (i.e. from 90 to 110%).  While this degree of variability is unlikely within a given lot, it is possible between lots.

 

Citations:

 

Thong MY, Manrique YJ, Steadman KJ. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices. PLoS One. 2018;13(3). Accessed online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832315/

 

Lee WM, Lugo RA, Cash J, Rusho WJ, Mackay M, Welkie K. The accuracy and precision of measuring Lorazepam from three liquid preparations. J Pediatr Pharmacol Ther. 2005, 10(1):36-42. Accessed online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468096/pdf/i1551-6776-10-1-36.pdf

 

Uddin, Md. Sahab et al. In-process and finished products quality control tests for pharmaceutical tablets according to Pharmacopoeias. Journal of Chemical and Pharmaceutical Research. 2015, 7(19): 180-185.  Accessed online at: https://www.jocpr.com/articles/inprocess-and-finished-products-quality-control-tests-for-pharmaceutical-tablets-according-to-pharmacopoeias.pdf

Libertas,

Great information. I knew that was variability between pills and lots. I believe it is more common than we know. I was wondering if this applies to the Brand as opposed to generic?

Thanks,

Dana

You’re welcome, Dana.  I have not been able to locate a credible source on the degree of variability allowed by the US FDA or United States Pharmacopoeia, but I’ve read other sources that suggest it’s in the same range as the Indian Pharmacopoeia.

Based on the conversations I’ve had with pharmacists and individuals who work in the pharmaceutical industry, my understanding is that brand manufacturers hold themselves to higher standards (e.g. +/- 3 to 5%).

Thanks, Libertas.

It makes sense. For us sensitive ones, I believe it makes it harder.

I have weighed my Teva which can range from .164-.176.

I then weighed my Roche brand 1 and 2mg and the weight was very consistent at .170-.172.

I realize that there is much more filler in the generic.

It would be nice to be able to see the API via some type of x-ray. I also wish I could tolerate the brand Roche because of the consistency. I found it to be very consistent. It was too strong and short acting.

I wonder if the .5mg would be better. I was taking Roche and Teva at the same time. Maybe that had something to do with it.

Again, thanks for the great information.

I agree with you, Dana.  Variability in the amount of API can and probably does cause issues for some individuals.  My hunch is that individuals who are tapering the more potent benzodiazepines (e.g. clonazepam, alprazolam) might be particularly sensitive to such differences.

Re: your comment about fillers ….

You might find the below-cited article of interest.  According to the author (a compounding pharmacist), “Excipients are functional ingredients that facilitate the therapeutic function of the API, not just inert ingredients [fillers] in a formulation.”  To illustrate her point, she presents an alarming example of how a change in excipients in the formulation of a commercially manufactured product caused significant patient harm.

Citation:

Ullman, P.  (2017). Excipient selection for compounded pharmaceutical capsules: they’re only fillers, right? Australian Journal of Pharmacy, Vol. 98, No.1164, pp.78-83. Accessed online at: https://www.medisca.net/pdf/published-articles/AJP%20Aug%2017%20-%20Practice%20Update%20-%20Excipient%20selection%20for%20compounded%20pharmaceutical%20capsules-%20they're%20just%20fillers%20right.pdf