H8fxr: Effexor what to do about the mini-tablets in generic capsules?

[H8FXR]

Brass Monkey Slide past 27.5mgai/91pw

 

 

10% taper

*all rounded to nearest mg

91mgpw/27.5mgai*90%=82mgpw/24.6mgai

 

slide

 

week 1 91−2.275 (2.5%) = 89mgpw

 

week 2 88.7 - 2.275 = 86mgpw

 

week 3 86.4 - 2.275 = 84mgpw

 

week 4 84.1 - 2.275 = 82mgpw

 

week 5 and 6 Hold

[H8FXR]

@brassmonkeyHey man, I need to ask a few things of you. Recently I've really been on a research kick and pouring over the patents for Effexor XR. An issue I can't seem to resolve is whether or not each bead has the same mgai.

 

I weighed until 25mgai/83mgpw, and I have realized that what I have been doing is inaccurate. The reason I believe this to be so is because the beads vary in size, small, medium, large. If they spill out randomly into the scale it will be a different number of beads every time. I see no evidence to believe that bigger beads have more AI. In fact, it seems more likely (from reading the patents) that all the beads start out as "core" or "active" beads (a mix of venlafaxine and methyl cellulose) and then are subsequently receive an XR coat or two (ethyl cellulose and hypermellose). That would suggest they all have the same amount of API regardless of size.

 

So its seems that counting IN beads is the way to go. Taking the same number each day. But I think pharmacokinetics have also to be considered. Since the capsules are filled with an assortment of bead sizes to achieve the proper dissolution rate over 24 hours, I feel the ratio needs to be respected as the dose is reduced. There is also information to support this in the patent.

 

One of my main concerns is that as one takes fewer and fewer beads the pharmacokinetics are thrown way off. After all the medication wasn't designed to be taken that way. I see a lot of members struggling when they are down to just a few beads and I don't think it's just to to larger drops in sert occupancy. 

 

What would you say to all this, I'm curious to know?

Cheers,

H8

Effexor XR patent: 

https://patents.google.com/patent/US6274171B1/en

[brassmonkey]

I think that you will find these two articles interesting.\:

 

(PDF) Pellets and pelletization techniques: A critical review (researchgate.net)

 

Comparing Drug Layering and Direct Pelletization Processes (pharmaexcipients.com)

 

Tapering with beads is a rather course way of doing it. It is essentially a linear taper that we are expecting hyperbolic results from. By reducing one bead at a time, we taper by a fixed rate instead of a progressively smaller one. We have proved time and again that the hyperbolic model is the preferred way to go because of SERT occupancy, bioavailability and a host of other reasons, but that is just not possible with bead counting. This is especially true at the lower doses, where the decrease of one bead massively out strips the percentage required. This linear method is why people using bead counting have so much trouble at the low doses. It is impossible to measure a decrease that is within the acceptable percentage.

 

Linear tapers, in this case bead counting, can work well to a certain point, if the person is not too sensitive to the changes. It is possible to follow a modified hyperbolic taper doing bead counting, but the dose will vary widely while doing so. Once the reduction rate passes 10% by removing 1 bead a different approach is required. The best method being to cross over to a liquid and follow the 10% rules. Switching to a liquid will result in AI dumping when the dose is consumed because it bypasses the time release part of the formulation, which can be a problem for sensitive people.

 

The difference in bead size can be a problem if you are strictly counting. If you are weighing the dose of beads, then the "rounding factor" involved in getting a full bead in the dose is the main variable. If a person is strictly counting, then a good mix of bead sizes is called for. Using all of one size could lead to being under or over dosed. But graduating size can be used to "refine" things at the lower doses. Unless a person is extremely sensitive to changes in dosage the differences in bead size would hardly be noticed even at the "one bead" level.

 

As far as bioavailability, absorption rates and the like go, each bead is pretty much the same in the way they act regardless of size.

[ChessieCat]

Instead of uploading documents which need to be downloaded, please use Google docs.  This allows the document to be viewed without the need for the program to view the document and also reduces the risk of computer viruses.  Sharing the Google docs link means that people do not need an account or password to access the document.

[H8FXR]

@ChessieCat thanks for the heads up - I will definately use Google Docs from now on.

 

Do you care to comment on the subject matter in my lastest post (the one above BM's)? Any input you could give would go a long way toward easing my concerns. TIA.

[H8FXR]

@brassmonkey Hey, thanks for your reply and the very interesting links - much appreciated! 
 

A little background: I began to doubt the accuracy of weighing when I met a member in a different group who was not only counting AND weighing but actually sorting her beads according to size. She’s very bright - so I was sure that she must be onto something. We teamed up to research the issue of bead size and tried to find a way to taper Effexor XR which makes the most sense.

 

Although she had the hunch a long time before me - we have discovered that size likely DOES matter. The smaller beads release the medication faster than the larger ones. What’s more, the patents seem to suggest that each bead has the same amount of active ingredient. If this is the case, a random assortment of bead sizes at a specific weight would yield WIDELY varying doses of venlafaxine. In this case, taking the same number of beads daily to ensure a consistent dosage would be wise.

 

By analyzing the size, weight and number of beads in Effexor XR capsules it looks like they may contain a consistent ratio of sizes. This is likely because the capsules contain a certain amount of each size to release the right amount of medication over time. So in order to preserve this property of the capsules it could be further helpful to take a certain number of small, medium and large beads.
 

Although it’s clear to me that at a certain point one can no longer taper hyperbolically or maintain the proper range of sizes, I am leery of a switch to an IR formulation. This could be risky considering dose dumping, a higher peak in blood plasma concentration, and changes in the pharmacokinetics in general. 
 

I just wanted to share what we have found in case anyone finds it helpful or is interested in knowing how bead size may factor into tapering.

 

Regards

H8

 

 

 

 

[ChessieCat]

This is in Post #1 of the Tips for Tapering Effexor topic:

 

  

On 5/6/2011 at 1:01 PM, Altostrata said:

 

At the end of the taper: Make a liquid from venlafaxine extended-release beads

If you have generic venlafaxine XR or Pfizer Effexor XR or Efexor XR in gelatin capsules filled with tiny beads, you probably will want to reduce by counting beads for most of your taper. But when you're down to 9 beads, how do you taper by 10%?

 

You can make a liquid with water from those beads. This has been proven to be stable (for 30 days) and effective: Rosa, N. F. D., & Sharley, N. A. (2008). Stability of Venlafaxine Hydrochloride Liquid Formulations Suitable for Administration via Enteral Feeding Tubes. Journal of Pharmacy Practice and Research, 38(3), 212–215. https://doi.org/10.1002/j.2055-2335.2008.tb00841.x

 

When the beads are dissolved in water or pharmacy liquid, the drug become immediate-release venlafaxine with a much shorter half-life. You may wish to take it 2 or 3 times a day (see the section above about immediate-release venlafaxine).

 

 

[H8FXR]

@ChessieCat Hey, thanks for providing link. I have already seen it and although it is great to know that it’s possible to make a liquid suspension from Effexor IR or even XR, I have several reservations for doing so.

 

First and foremost I think it is a huge change for the mind and body to adjust to. Even switching brands is disruptive for some. With XR to IR, there is a possibility of dose dumping and experiencing an unpredictable and possibly disastrous adverse reaction. Dissolution studies in the patent indicate that IR has a significantly higher peak for blood concentration over XR - I wonder how one might react to that. Also, the pharmacokinetics are very different: IR peaking in ~2hours and rapidly dropping off to sub-therapeutic levels by 12 hours, needed an additional dose - right before bed time no less. XR peaks in about 6+/-2 hours and gradually falls over 24 hours.

 

It seems feasible but I think it may be quite destabilizing and hard to predict how one will react. Wouldn’t it be better to switch to IR (crushing and weighing a mini tab for example) at a higher dosage when these kinds of changes do not have as much of an impact on serotonin occupancy? Are there many members that you know of that have had success with a switch to liquid at a low dose?

 

Regards,

H8

[ChessieCat]

I can understand your concerns, but was just letting you know about it because I had only just noticed it myself and I've been a mod for 6 years now.

 

It is good to know what options you have available when you get to the lower doses, especially if you are not able to get prescription liquid or immediate release tablets and not able to tolerate reducing by a bead at a time.  And to get used to the immediate form of the drug you could start by dosing every few hours and then gradual bring it back to 3 times a day.  Obviously you would only use this method if you really had no other options.

 

Pristiq tablets cannot be dissolved in water because they go lumpy and I did most of my taper using compounded tablets.  It wasn't until right at the very end of my taper that I discovered that I could dissolve the contents of a capsule (compounded) in water.  If I had known this at the start of my taper it would have made it easier to get my doses and probably would have ended up saving me money.

[H8FXR]

@ChessieCat

I am glad I reached out to you, because you have shared something I did not think of - namely, to dose more often and scale it back. So thank you for that! 

 

it still seems like a wild ride - venlafaxine roller coaster…I guess I will have to look over more cases to get a feel for how people react, but there seems to be a dearth of info on it unfortunately.

 

I am surprised to learn that Pristiq goes lumpy in water. I know that it is made differently than Effexor. I think there are the same issues with some generic varieties of venlafaxine mini tabs. Did it go lumpy after being crushed completely to a powder first and then dispersed in water? I would think that is what the compounding pharmacy does… shear the tablet into powder and fill into capsules. Thanks again for the info.

 

Regards,

H8
 

 

[ChessieCat]

6 minutes ago, H8FXR said:

Did it go lumpy after being crushed completely to a powder first and then dispersed in water? I would think that is what the compounding pharmacy does… shear the tablet into powder and fill into capsules.

 

Yes, it's because there is a glue in the tablet which extends the release.  The pharmacy ground the tablets to a fine powder and added fillers.  When added to water I would shake it up thoroughly and then let it sit for at least an hour to settle all the bubbles caused by the fillers.  After it was made up I would just gently stir the mix before syringing out my dose.

 

And another thing with the DIY Effexor liquid is that you can always use it to take with beads to make up the dose you want if needed.

[Bindy]

On 3/3/2021 at 1:50 PM, H8FXR said:

TLDR: switched from 75mg/D Sandoz (generic) Effexor XR to 75mg/D Wyeth (brand-name and with beads) Effexor XR. Doctor did not support bead counting/wieghing; suggested alternating dose regime and then Pristiq. 

 

UPDATE: M36, 75mg/dEffexor XR. I saw my doctor after the two week period in which I was supposed to bridge to trintellex (which I didn't take) for the purpose of cross-tapering. For two weeks I steeled myself to go in there and succesfully switch from generic Effexor XR containing mini tablets to the Wyeth brand name Effexor XR with the beads so I could do the 10% taper. My hope was he would be on my side and support it.

 

I told my doctor I couldn't tolerate the Trintellex and right away we begin discussing tapering Effexor. I told him straight away I would like to switch to beads and proposed titrating the dosage 10% (hyperbolically) by compounding the capsules by weight in lower dosages. He was against it, saying that the time release mechanism would be compromised. I responded that I had looked at the patents and the the extended release was an enteric coating on the microspheres.

 

He quickly moved the conversation away from what I presume he thought was "tampering" with the medication. I acknowledge that he may not want to be liable for endorsing it.

 

He suggested I achieve a 10% reduction by filling my script with 37.5mg capsules and taking 2 37.5mg capsules for 3 days and then just one 37.5mg capsule for one day and then back to two or 3 days. I told him I don't follow how that would be a 10% reduction. He said that the medication "bioaccumilates" and that I wouldn't fell to much on the low dose day. I told him I would surely be a mess on the off day because of the short half-life of the medication and I feel this would be playing ping pong with my brain. He said I could dose a half-tablet twice a day because the 37.5mg capsules are immediate release. I asked him if he was sure, because afaik IR was discontinued. He looked it up and agreed and he had a chance to see that Pristiq was related to Effexor and also available.

 

So then he started exploring the possibility of switching to Pristiq. I told him I've looked into it and since it is also extended release and similar if not stronger than Effexor this would not help tapering. I promptly apologized for all the push-back, and explained that I had been researching this a lot and getting off Effexor was extremely important to me.

 

He then steered the conversation back to the alternating half-dose day and it began to look like that was my only option. Furthermore he was proposing I use the current generic caps with the mini-tablets. So as a last resort I asked him if I could switch to the brand name at the current 75mg/d dose and see how that goes. He said that's a good idea because they are not bioequivalent and I would need an adjustment period. Great - I feel like at that point he just wanted to get me out of there. So he filled the script and I got the beaded medication of my heart's desire.

 

I'm going to take it as prescribed at 75mg/D for 4 days or so while I wait for my jewellers scale to arrive and so that I can establish whether its effect is much different than the previous generic brand.

 

The bad part is that now I feel like I have to keep it hidden from my doctor that I'm self-titrating the medication. I'm pretty sure he will have figured out that this was the end-game of my visit anyway. It's now and awkward situation because if I need his support or any helper meds (god forbid) it will be difficult if I don't tell him what's actually going on. I'm prepared to do it alone but it sure would be nice if he was supportive of this unorthodox method of tapering. 

I am really proud of you. You can do this.

I was a t 150 mg and basically took 2 beads a day then 4 and 6 etc. It was tedious but I started in Nov 2022 and by Feb 2023 I was at zero mg. The first 2 to 3 weeks at zero were ruff but I honestly think there is no way around it. I took some great natural supplements but not sure if I am allowed to discuss on this forum. I luckily found an amazing doctor who supported me he was a MH and behavioral Physicians Assistant. I used some klonapin very sparingly and now very rarely. My biggest challenge is sleep these days. Although in my case I am currently officially in Menopause so some extra challenges.

Every person's experience and challenges going off antidepressants is different but I think Effexor is one of the worst. My Dad's wife is a Psychiatrist in Canada and she totally agrees with me on that.

 

A great resource is a lady on utube name Angie Peacock. I hired her for a 30 min consultation and she really validated me that I wasn't loosing my mind.

 

Your doing great keep strong and sending positive vibe your way H8fxr.