Mirtazapine - stability-tested liquid formulations

[[Fa...]]

I am not yet ready to taper this medication; however, I plan on using a stability-tested liquid formulation when I do so.  Does anyone have any input on this matter (nudge @[Li...])?  I figured this topic may assist someone other than myself as well.  Thanks in advance.

[[Li...]]

Consider me nudged, @[Fa...].

What sort of input are you seeking?   It would also be helpful to know your current dose and dosing schedule. 

[[Fa...]]

Haha, thanks @[Li...].  I guess it would be helpful to know my dose and dosing schedule.  I dose 7.5mg once daily in the evening.  Dosing duration of 10 months.  It was a risky off-label 'taper aid' addition with of little perceived desired effect - improved sleep.

I know the first, and most imperative, step is making sure you feel comfortable with your pharmacist.  In the US, having PCAB accreditation and being a PCCA member pharmacy are ideal.  My current local pharmacist for example I feel extremely comfortable with - he is a PCCA member; however, it does not appear he is PCAB accredited.  There is another local pharmacy I feel comfortable with that is PCAB accredited.  I am not currently using them as they were unable to stock the Hikma diazepam oral solution I had requested.  Links below.

https://www.pccarx.com/Resources/FindACompounder

https://a4pc.org/find-a-compounder/

With that said, I would still feel most comfortable if there was a known 'tried-and-true', stability-tested liquid formulation in existence that I could reference for my pharmacist.  In addition, a suggested mg/mL ratio would be ideal.  I would assume a ballpark figure for my scenario would be at the most a 5mg/mL suspension - perhaps closer to 2mg/mL for accuracy purposes as I decrease. 

[[Li...]]

Hello again @[Fa...].  Thank you for the clarification.  The good news is that formulations for both solutions and suspensions exist (see list and comments below); the bad news is the concentrations of two of these formulations are higher than what you need to implement a symptom- and functionality-based taper from your current dose of 7.5mg.

In your shoes, I would call both of the pharmacies you’ve identified to ask if they have access to a stability-tested formulation in a suitable concentration. Given that you are accustomed to working with a liquid with a concentration of 1mg/mL, I wonder if that might be worth considering? However, let me hasten to add, I have not researched the potency of mirtazapine so have no idea if that low of a concentration would be needed.

You also might consider contacting Shawn Gill (a Canadian PharmD and compounding pharmacist) to ask if he knows of stability-tested formulations for liquid mirtazapine.  As of spring 2023, Shawn was a clinical advisor for Outro Health, a digital healthcare service dedicated to helping individuals safely discontinue antidepressants. Here’s the link to his LinkedIn profile:
https://ca.linkedin.com/in/drshawngill

Links:

Mirtazapine 15 mg/ml Oral Solution
Summary of Product Characteristics (SmPC)
https://www.medicines.org.uk/emc/product/2023/smpc/
(This is from a UK based speciality pharmacy.  I’ve included it here for two reasons.  First, it demonstrates that it is indeed possible to formulate a mirtazapine solution.  Second, it gives us insight as to the excipients required to do so: l-methionine, sodium benzoate, saccharin sodium, citric acid monohydrate, glycerol, maltitol liquid, tangerine flavour, and purified water.

Mirtazapine Compounded 10mg/mL Oral Suspension, Veterinary
https://doi.usp.org/USPNF/USPNF_M11863_05_01.html
(Regrettably, the complete formulation is not available online; however, it has been vetted and approved by the US Pharmacopeia so a reputable compounder should be able to gain access to it.)

Mirtazapine 7mg/mL Oral Suspension,SpectrumRx
https://cdn2.hubspot.net/hubfs/471158/LAB_DOCS/Mirtazapine_Suspension_Oil.pdf
(I have no idea if this is a reputable outfit or not. As stated on the formulation “No claims are made as to the safety or efficacy of this preparation. This formulation is provided solely at the unsolicited request of the pharmacist.”)

[[le...]]

Can I just ask how you felt when you first took this. I’ve been taking 15 mg fir 5 days and feel terrible. I literally cry from about a hour of waking up solidly until when I go to bed. Taking it fir anxiety and intrusive thoughts. Prior to this had bit meltdown fir few hours most days but not literally crying all day and so depressed. Wondering if it is something goes off after couple weeks. Am going to try halving the dose as I am very sensitive to meds,

[[Fa...]]

Thank you as always @[Li...] for your insight and feedback.  I appreciate it more than you know.  I will report back once I have spoken to my pharmacist and have something to report.  FWIW - when I do decide to begin the taper, I will most likely proceed confidently with a .5mg cut (6.7% reduction) and continue with .5mg cuts until my body tells me otherwise.  With this in mind, I would assume a slightly higher concentration than 1mg/1mL would be suitable (and more economic) - particularly at the beginning of my taper (and hopefully the duration).  

The fact that it had little to no perceived effect on me at 7.5mg, and also a very 'low' dose - I consider this to actually be good news in terms of discontinuation.  From what I've read of people's experiences, it seems that these individuals in general have an easier time.  Those that mirtazapine had a profound effect on (i.e., stabilization from benzo withdrawal, notable improvement in sleep etc...) seem to be the individuals that more often than not encounter issues when discontinuing.  Again, this is just my opinion.

@[le...] I'm truly sorry you are having a tough time.  As I stated above, the 7.5mg dose of mirtazapine had little to no effect on me - though it is basically nothing more than a potent antihistamine at this dose.  I wish I could be of more assistance, but my experience is that it is as if I am taking nothing when I dose 7.5mg once daily in the evening.  It may have helped my sleep slightly, though for the most part, I have no perceived positive or ill effects.  I would recommend speaking with your doctor about your situation before halving your dose.  He/she may suggest you 'give it more time' before making changes or even to discontinue it completely with your stated adverse effects.  

[[Bo...]]

@[Fa...]

did you determine your Mirtazapine liquid yet? Curious what your pharmacist suggested…. I just had my compounder make one up with the suspension vehicle used for my liquid Klonopin I finished in August.
 I hope that will be ok to use. It was stability tested for Klonopin. 
@libertas 

[[Fa...]]

Hi, @[Bo...].  I have paused my initial research and discussion with my pharmacist regarding the Mirtazapine.  The discussion is trending in the right direction however.  I am leaning towards a 1mg/1mL concentration.

Below is my last correspondence with my pharmacist in which I have yet to respond.  When I do, my reply will include at least two additional questions such as shelf life and pricing.  Please do let us know what you discover as well.

Update from pharmacist:

I would be able to make the concentration that you requested, in fact, any concentration is possible.

I would be the one to make it each time for consistency.

The stability would be literature tested so that would solve that issue.

Mirtazapine would be made from ODT (orally disintegrating tablets) from the same company each time.

So, I think that we can meet your requirements for every question that you have.

If you think of anything else, feel free to contact me.

 

[[An...]]

@[Fa...] This is fascinating and so much important information. 

Does your pharmacist mean that he or she is able to use orally disintegrating tablets to make the solution? If so, this is very important because I seem to have trouble switching manufacturers. I would benefit greatly from a solution made with the orally disintegrating tablets that I am taking.

Thank you for sharing this correspondence. I have a good compounding pharmacist, but he has never mentioned this option. 

[[Li...]]

@[An...] I’m glad you bumped this thread.   My guess is that @[Fa...]’s compounding pharmacist is proposing to make a suspension using the orally disintegrating tablets (ODTs) and a suspending vehicle but I’ll look forward to his response.

@[Fa...] Are you currently using regular tablets or ODTs?  If the former, have you considered a trial of the ODTs to see if they agree with you before you switch to a liquid made with them?  (Knowing you, the answer is probably “yes”.)

@[Bo...] Congratulations and well done on getting a compounded liquid! Are you feeling any better?  Please let us know if you need assistance with developing an initial taper schedule to try. You know the drill.  We’d need to know (1) your target taper rate and reduction interval, (2) your daily dosing schedule (amounts and times) and (3) the concentration of the liquid. 

[[Fa...]]

Hi, @[An...] and @[Li...].  I'm sorry I do not have more information currently, but I will certainly convey information as I receive it.  I am almost one week into switching a portion of my diazepam tablet dose to liquid with the intent of reducing only this medication for the time being.  I'm doing well, but am not too keen, or willing, to reduce 2 medications concurrently at this time.

With that said, my plan is to have all of my 'ducks in a row' when the time comes to discontinue mirtazapine.  When I have time, I plan on responding to his last correspondence with another series of questions and will report back.  I assumed this process would take a while to get the information I desired without overly 'frustrating' him and remain tactful in my approach. 

I too believe my pharmacist is proposing making a suspension using the orally disintegrating tablets (ODTs) and a suspending vehicle.  @[Li...], I have not yet trialed the mirtazapine ODTs for reasons stated above - but best believe that is in the plans if I proceed with his 'literature stability-tested' formulation using them.... and with a month+ supply of existing tablets on hand prior to switching.  With that said, I highly doubt I have an issue with the switch, but it is certainly wise to do such a trial.

@[An...], perhaps you could ask your compounding pharmacist if he knows of, or can look into locating, any stability-tested formulations in which he could use your ODTs to prepare and report back to us?