Tips for tapering off Zyprexa (olanzapine)

[Altostrata]

ADMIN NOTE Also see Dose Equivalents for Second-Generation Antipsychotics

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Olanzapine is an atypical antipsychotic with a number of serious drug interactions and side effects, weight gain, blood sugar elevation, and movement disorders among them.

Official FDA information at http://www.drugs.com/pro/olanzapine-tablets.html

To minimize the risk of withdrawal symptoms, we recommend a conservative taper of 10% from the previous dosage every few weeks. The amount of the decrease keeps getting smaller. Some people find they can go faster and some people find they have to go slower -- they can only tolerate decreases of a fraction of a milligram at a time. See Why taper by 10% of my dosage?
 
Very careful tapering is necessary when you have had psychotic symptoms. Withdrawal symptoms that look like psychosis can appear even in those who never had psychosis. If you have a prior diagnosis of psychosis, emergence of these symptoms from dopamine supersensitivity can cause you to become diagnosed as "relapsed" and re-medicated. Read Psychiatrist: Some patients are better off without antipsychotics...

Fortunately, olanzapine comes in a range of dosages for tapering, from http://www.drugs.com/ppa/olanzapine.html

Quote

Zyprexa
- Tablets 2.5 mg
- Tablets 5 mg
- Tablets 7.5 mg
- Tablets 10 mg
- Tablets 15 mg
- Tablets 20 mg
- Injection, powder for solution 10 mg

Zyprexa Relprevv
- Injection, powder for suspension, ER 210 mg
- Injection, powder for suspension, ER 300 mg
- Injection, powder for suspension, ER 405 mg

Zyprexa Zydis [wafers]
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg
- Tablets, orally disintegrating 15 mg
- Tablets, orally disintegrating 20 mg

Novo-Olanzapine (Canada)

 
Olanzapine's half-life ranges from 21 to 54 hours  -- from https://www.ncbi.nlm.nih.gov/books/NBK532903/

 

Quote

Absorption: Daily administration of olanzapine leads to reaching the steady-state plasma concentration in about one week. The time to peak concentration is 6 hours for oral formulation and 15-45 minutes for IM formulation. Olanzapine has a half-life of 21 to 54 hours, with an average of 30 hours.

.....

 

Metabolism: Olanzapine is extensively metabolized by the liver by glucuronidation and the cytochrome P450 system. This system's enzymes that metabolize olanzapine are primarily CYP1A2 and, minorly, CYP2D6. CYP1A2 genes are poly-morphic; however, a study showed no reported associations between various polymorphisms and pharmacokinetics of the medication.[10][11]

 

Excretion: The half-life of olanzapine is approximately 30 hours (varies between 21 to 54 hours). Olanzapine is excreted primarily via the renal route (57%) and feces (30%). 

 

 

Given olanzapine's half-life, it's possible your body will not even recognize a change in dosage for 2 weeks. Then we advise another 2 weeks of observation to make sure that withdrawal symptoms do not develop, which indicates olanzapine should be tapered no often than monthly.

Using tablets to taper
Since olanzapine comes in many dosages, at least initially, tapering can take place using tablets and splitting them. Plan your taper and, via prescription, convert any dosage to some number of lower-dosage tablets.

Zyprexa tablets can be safely split, according to http://ps.psychiatryonline.org/article.aspx?articleID=84368
 

Quote

patients should be cautioned that because of the coating of Zyprexa, split tablets must be used within seven days.

 

summed up at http://depression.about.com/od/depressionmedication1/a/savemoneyonmeds.htm
and Consumer Reports http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/money-saving-guides/english/PillSplitting-FINAL.pdf
 

However, the tablets can be difficult to split because they tend to be very small.

Use a digital scale to weigh tablet fragments
To control your dosage more exactly, you may wish to weigh tablet fragments, see Using a digital scale to measure doses
 
Pharmacy compounding of capsules or liquids to taper
At a very low dose of olanzapine, if you are sensitive to dosage reductions, you may wish to request a prescription for customized capsules or a liquid from a compounding pharmacy. This will enable tapering by a fraction of a milligram.

 

Ordinarily, to make customized capsules, a pharmacy will crush tablets, weigh the powder, and put a specified dose in each capsule.

A pharmacy compounding formula using crushed tablets to create a liquid suspension is here http://www.pharminfotech.co.nz/manual/Formulation/mixtures/olanzapine.html
It is also attached to this post. (It notes olanzapine is "practically insoluble in water.") This formula says the suspension will expire in 14 days.
 
You will need a prescription written for custom compounding. The only drawback is this can be quite expensive.
 
Using a liquid to taper: Make your own liquid
However, like other drugs that are not particularly soluble, you can make a suspension, as our member Rhi explains. Also see http://survivingantidepressants.org/index.php?/topic/2693-how-to-make-a-liquid-from-tablets-or-capsules/

According to http://www.pharminfotech.co.nz/manual/Formulation/mixtures/olanzapine.html

Quote

Olanzapine (as crushed Zyprexa^® tablets) is stable for up to 6 hours at room temperature and up to 48 hours refrigerated in water and the following beverages; orange juice, apple juice, cola and milk.

 

The preparation and stability of a liquid olanzapine preparation for oral administration in hospitals

The Pharmaceutical Journal Vol 265 No 7110 p275-276 August 19, 2000

 

Quote

 

....We have found that Zyprexa tablets 10mg, crushed and suspended in Guy's hospital "paediatric base", provides a more palatable liquid oral olanzapine preparation than crushed tablets suspended in water.

....

Zyprexa tablets (3 x 10mg) were halved and then crushed using a mortar and pestle and the powder suspended in 30ml Guy's hospital formula base for paediatric mixtures (paediatric base), a syrup-based mixture containing carboxymethylcellulose BP, methylhydroxybenzoate BP and propylhydroxybenzoate BP.3 Each batch of olanzapine suspension was stored at 2?8C in a 50ml amber glass bottle in the dark.

....

The suspension settled quickly and powdered tablet fragments formed a visible layer on the bottom of the glass bottle. Experience with the analogous clozapine suspension3 has shown that the need for vigorous shaking must be emphasised to nursing staff who may be asked to administer the suspension to patients. As with the clozapine suspension, informal assessment of the palatability of the olanzapine suspension has shown it to be well tolerated, some patients in fact preferring it to tablets.

....
No tests of microbiological stability have been performed although paediatric base is preserved. It therefore seems prudent to recommend a shelf-life of two weeks when the product is stored in a refrigerator. Such a shelf-life is adequate for hospital use. We have no information on the bioavailability of olanzapine from the suspension, although it seems unlikely that olanzapine bioavailabilty will prove to be less than that from Zyprexa tablets.

 

 

Guy's hospital "paediatric base" appears similar to Ora-Plus suspension base, which is commercially available:

 

http://www.perrigo.com/files/rx/pdfs/pds173-ORA-Plus.pdf

 

Quote

....ORA-Plus is an aqueous-based vehicle consisting of a synergistic blend of suspending agents that have a high degree of colloidal activity. The suspending agents form a structured, gel-like matrix which suspends particles and allow for little settling. ORA-Plus is buffered to a slightly acidic pH to help reduce degradation of medicinal agents through oxidation. An anti-foam agent is incorporated in ORA-Plus to allow for vigorous shaking with minimal foam.

 

Ingredients

Purified water, microcrystalline cellulose, carboxymethylcellulose sodium, xanthan gum, carrageenan, calcium sulfate, trisodium phosphate, citric acid and sodium phosphate as buffers, dimethicone antifoam emulsion. Preserved with methylparaben and potassium sorbate.....

If you want to experiment further with dissolving the tablet:
 
https://www.caymanchem.com/pdfs/11937.pdf

 

Quote

Olanzapine is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, olanzapine should first
be dissolved in DMSO and then diluted with the aqueous buffer of choice. Olanzapine has a solubility of approximately
0.5 mg/ml in a 1:1 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend storing the aqueous
solution for more than one day.

 

Example of a do-it-yourself liquid method: 

 

 

Using orally disintegrating Zyprexa tablets or wafers to taper
Orally disintegrating tablets (ODT) or wafers, which dissolve in the mouth, come in a range of dosages (see above). Conceivably, one might very carefully cut up the wafers to taper, but they may be difficult to cut accurately. (I haven't done this and don't know of anyone who has, please let us know if you try this.)
 
Making a liquid with water would seem to be a better way to taper utilizing these tablets or wafers.

 

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-5949.2008.00053.x

Quote

"The orally disintegrating tablets may be placed in the mouth or dispersed in water or other suitable beverage for administration (data on file: Eli Lilly and Company). Stability of the orally dispersible tablet formulation was tested in water, apple juice, orange juice, coffee, milk, and cola beverages, and it was found that a stable suspension formed with each of these beverages except cola. The suspension with apple juice, orange juice, coffee, and water is stable at room temperature for 6 h. All of these suspensions are also stable under refrigeration for 24 and 48 h. Coffee was not tested under refrigeration at any time period. The suspension in milk is stable for 6, 24, and 48 h under refrigeration. A precipitate forms when the orally disintegrating tablet is mixed with cola; therefore it is not recommended that orally disintegrating olanzapine tablets be mixed with cola beverages. At the time of this report, evaluation of the efficacy and safety of extemporaneous preparation administration has not been conducted."

 

This also applies to Zyprexa Velotabs, as specified in the European patient instructions for these wafers.

One of our members has tapered successfully by making a liquid with the orodispersible wafers, see http://survivingantidepressants.org/index.php?/topic/3743-tips-for-tapering-off-zyprexa-olanzapine/?p=163188
 
You can refrigerate the liquid  for up to 48 hours in a clean, capped tinted containing, safely discard any left over after that.
 
Using a combination of tablets or capsules and liquid
Rather than switch directly to an all-liquid dose, you may wish to take part of your dose in liquid and part in lower-dose tablets or capsules, gradually converting to all liquid as you get to lower dosages. This can be very convenient and reduce any problems switching from one form of the drug to another.
 
If your doctor prescribes compounded liquid and tablets or capsules at the same time, most likely he or she will have to indicate "divided doses" in the prescriptions to get the drugs covered by insurance.

 

Attachments:

 

180329 Formulation_mixtures_olanzapine.pdf

 

 

Edited January 25 by Altostrata
updated

[Jerome]

Hi, Alto: Looking at the "Formulation in Pharmacy Practice" prep, these are directions for making a suspension, probably because olanzapine is not very soluble. It is quite soluble in DMSO (15 mg/mL, Sigma-Aldrich) and that's probably the only direction to go in if you need a solution. DMSO is regularly taken safely in oral solution. However, I suspect many people will prefer an alternative, if one is available.

 

These directions are similar to the ones given in the APhA Handbook for clonazepam--the benzo is suspended in a very viscous syrup to keep the particles evenly distributed, the same basic thing that Ora-Plus does. I'm not familiar with carboxymethylcellulose or with preparing syrups, but I assume that the medium they describe here would keep the drug evenly suspended so that it's distribution would be homogeneous and it could then be measured accurately. I hope this helps. Aweigh

[Altostrata]

Wow, thanks, Jerome. That will help many people figure out how to taper olanzapine.

 

Do you think the suspension in water would be even enough for tapering?

[Jerome]

Hi: You're welcome. I hope it does help people taper from Zyprexa, and suggest that the same methods might be applicable to clonazepam, another benzo that has solubility issues.

 

At the bottom of the linked suspension prep there are two references. The first one, from which the prep is probably taken, has a link to the full article. It looks to me like you can pay to get it on line or go to the library and copy it from the Royal Journal of Pharmacy. I'd want to read the full article before preparing and swallowing the syrup. The article is titled "The preparation and stability of a liquid olanzapine preparation for oral administration in hospitals", so I think it should be suitable for tapering as long as the viscosity doesn't cause measuring problems. If it does, they can be overcome.

 

 

Aweigh

[Rhiannon]

I'm kind of out of it right now and need to go to bed, but I just wanted to toss in my usual bit on the subject of making preparations for liquid tapering, which is: I personally don't worry about solubility.

 

None of the meds I'm tapering are actually soluble in water. But the pills dissolve into small enough particles that I can stir them up and keep them suspended in water while I measure them out, and that seems to work for me. I stir well before I measure, I stir a little while pipetting them up; I dissolve the pills in glass and pipette out of glass so that I can see visually how evenly everything is suspended, and that's good enough for me.

 

I use water as a medium because I like it that I can easily see for myself how evenly the little particles are suspended or if they seem to be settling out. Also because it's handy and cheap and I don't have to carry it with me if I travel.

 

Mostly I would just say, I don't think it really matters if the medication is soluble in whatever vehicle you're using, as long as it can be evenly distributed. What really matters is that it be evenly distributed and that your method be repeatable and consistent.

[Altostrata]

Thank you for that excellent advice, Rhi.

[Jerome]

Hi, Rhi:

And thank you, Altostrata. Rhi, I still don't have the hang of following threads and how notification works [maybe I have to set them?], so I didn't see your reply until just now. It's very amusing, to my sense of humor, that our first conversation was about this very subject on BB last Sept. I would like to have a go at solutions, suspensions, dispersions and their ilk...some other evening. My lack of faith in my own ability [dexterity] to consistantly titrate in a water suspension as you describe so well may have lead me to...alcohol I did try milk first, but I think it didn't work for me 'cause I didn't believe in it. Reverse placebo effect.

 

Right now, my taper seems to feature sleepiness as the most prominent sx, along with mood changes. Is there any way that could be an ID w/d effect? Because I think the IDW may be happening, but sedation seems counter-intuitive.

 

And a good night's sleep to all,

 

Jerome

[Altostrata]

Good for you that you're sleepy instead of the opposite. I'd view that as your body's restorative functions kicking in.

 

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[Tuskentank]

Does anyone know if the orodispersible wafers would allow for a liquid solution with water. These are designed to dissolve on the tongue so I'm figuring this would work with water?

[Altostrata]

Is this what your wife has been putting in your tea?

[Tuskentank]

Hi Alto, no she's been dissolving the ordinary tablets. 5mg over 5 weeks to date. I tried this myself with one last night and it seemed to dissolve reasonably well. I'm so scared right now. I was going to do a micro taper each day over 3 months given the short spell I've been on them.

[Altostrata]

How short a spell and what kind of dosage?

[Tuskentank]

HI Alto, it's been 5 weeks at 5mg a night. My family expect me to just get over this and keep threatening that my wife will leave me and take the kids. They think my reactions to this are a sign of psychosis. When I confided that the diazepam withdrawals were making me suicidal, and told my mother that I had phoned a helpline, she told me to get a life. This is all so ludicrous, but true that it is killing me. I am fighting this on my own. I spent the entire summer being tried on different anti-psychotics against a backdrop of my wife threatening to leave me and take our kids, and the deterioration this caused to me, and then been told they slipped the olanzipine in there because my way hadn't worked. I wish I didn't hate them so much right now.

[Altostrata]

I'm sorry you're having such a bad time with your family. I would be very angry with anyone who thought I was deluded.

 

If you've been taking any psychiatric drug for more than a month, you're at risk for withdrawal syndrome, and you'll want to reduce very carefully until you find your tolerance for dosage reduction.

 

I updated the first post in this topic to include the orodispersible wafers.

[LaurensOn]

Hello. My name is Lauren and I'm looking for a little help. I have been taking 2.5 mg of zyprexa for one year now. I want off it so badly. I've tried twice but once I start to feel funny I immediately go Back to taking it regularly. I'm in the middle of trying again this week and came across this site today and it looks as if I'm doing things all wrong. I've been taking the 2.5 every other night instead of every night for one week now. I'm not sure what to do next. Today, I don't feel well. I feel agitated, foggy, and nervous.

 

Since it's only 2.5 the pills are already quite small. In addition, they are not flat, round pills. They have a bit if a circular shape to them.

 

Since taking zyprexa, I've gained a lot of weight and my cholesterol has become borderline high.

 

I just don't know what to do anymore, this is very difficult! Any help or advice is appreciated.

[Meimeiquest]

Hi Lauren,

 

I'm a Zyprexa survivor...it can be done! Why don't you write a full intro with signature in the intro and update forum, especially if you are on other meds. I've made a lot of mistakes along the way, but tapering Zyprexa first was, for me, the most serious of them. I'm assuming you read this thread on Zyprexa tapering?

[LaurensOn]

Hi Meimeiquest!

 

Thank you SO much for replying to me, it meant the world to me tonight!

I'm so happy to hear that it can be done, thanks for sharing that.

As I sit here and not feel well I simply cannot tell if it's a withdrawal symptom.

 

I will do what you said about writing an intro and signature as soon as I get my son to bed.

 

I read enough of the zyprexa tapering instructions to know I am doing it wrong, but I need to read it more closely this time.

 

Lauren

[Tuskentank]

HI Meimequest, do you mean it would be better to taper zyprexa after other meds? I was thinking of a daily taper with minute reductions each day.

[Meimeiquest]

Generally it is best to taper from most activating to most sedating. But given the short time you've been on Zyprexa, I think it is an Alto question. I have never heard of a micro taper for Zyprexa, but that doesn't mean it couldn't be done.

[Tuskentank]

Hi folks, I'm thinking a daily microtaper might be easier on the CNS? Given olanzipine's 17 receptor hits I was thinking this might make for an easier taper. Is there anyone who does microtapering? Looking for some encouragement to get off this junk.

[Laqiya]

The orodispersible wafers were the ones I was on, not the Olanzapine tablets. (Was confused about this before) The lowest available dose to be found was 5mg and had to halve it further to 2.5mg. Although I couldn’t really get it cut accurately since it disintegrates easily when breaking it in half so maybe the dosage would vary each time.

 

I suppose you could do the same microtaper with wafers just like tablets?

 

Since it can be easily made into a fine power, it‘s better dissolved than the tablets, I guess. Does that mean it’s more soluble in a liquid like water for the purpose of tapering minute amounts, though? I don’t know.

 

I’m interested in learning how to taper this drug as well. Thanks for adding in the new info.

 

[Altostrata]

Tuskentank -- yes, you might try a microtaper.

 

Laqiya -- making a liquid from the wafers seems to be a good way to taper. Instructions for doing this are in the first post.

[Tuskentank]

Just an update. I made a liquid solution with water and the orodispersible tablet. It forms a perfectly even solution so a daily taper should be accurate.

[mammaP]

I'm glad you found the wafers are good for your taper, and hope it goes smoothly for you. 

[Meimeiquest]

Is it confirmed that the dissolved wafer and dissolved tablet bioavailability are the same? I'm not saying it's not, I just think we need to be sure.

[Altostrata]

You'd have to ask a pharmacist about that one. It's pretty clear being put in water doesn't affect wafer bioavailability. People seem to be doing fine making suspensions of other drugs with water.

[Meimeiquest]

My concern is that the wafer is made to pass directly through the mucous membranes into the blood, whereas the tablet is meant to undergo first pass metabolism by the liver. If you swallow the wafer in water, theoretically it will not be absorbed till it hits the GI tract. Which may or may not matter.

[Altostrata]

The mouth, throat, stomach, etc. are all lined with mucus membrane. You're right, the direct absorption through mucus membrane is faster, which is why sometimes when switching from tablets to liquid, the dosage of liquid preparations needs to be adjusted downward slightly.

Olanzapine orodispersible tablet is bioequivalent to olanzapine conventional tablets, with a similar rate and extent of absorption. It has the same dosage and frequency of administration as olanzapine conventional tablets. Olanzapine orodispersible tablets may be used as an alternative to olanzapine conventional tablets.

[Tuskentank]

HI all, I'm confused. Does this mean that by dissolving the wafers I've effectively already taken a cut?

 

I tried the traditional 10% cut and things have been pretty bad in terms of anxiety, but a bit better today, although not great. Going to hold my diazepam, fluoxetine and olanzapine for a few weeks at least at the current doses, then look at daily tapering of the wafers. My only concern is that diazepam lowers serotonin, so would leaving this to last mean my receptors wouldn't grow back properly? I'd love Rhi to advise on this as she's  been tapering citalopram and diazepam.

[Altostrata]

No, the wafers are equivalent to the tablets.

 

Do you feel any differently?

 

Don't worry about your serotonin receptors. All receptors tend to self-correct over time.

[LongJohn]

10% reduction/month seems like a good starting rule.  At what level might it make sense to "jump" off?

[Meimeiquest]

I think you will know when you are ready to "jump." You can read Hudgen's thread on how he went off an AD at the end. I went off at 0.6mg before I came here...that was way early. But I lived . Rhi is having good success with dropping several together in tiny amounts, Rhiannon is the name of her introduction.

[Katy91]

I am using orodispersible  olanzapine to taper.  In the UK it is available in 5mg, 10mg, 15mg and 20mg tablets.  

 

I dissolve 5mg in 100ml of water in a measuring jug then syringe out what I'm reducing by.  The syringes are available free from the pharmacy.  I let the tablet dissolve for a minute then I stir with a teaspoon, as though it dissolves well the particles tend to gather at the bottom, then I quickly syringe out what I what to get rid of.  At the moment I'm syringing out 11ml of liquid meaning I'm on a dose of 4.45mg.

 

I wish that more people knew about orodispersible olanzapine as I only found it after much research.   Trying to accurately cut the tiny regular olanzapine tablets is really impossible whereas using the orodispersible tablets is a very easy and accurate way to taper. I use a 5ml syringe which has measurements of 0.5ml on it, meaning I could taper by as little as 0.025mg if I liked.  I am actually tapering by 0.1mg a week and so far so good.

 

I must point out that the orodisperable tablet is not the same as the velotab/wafer.  The velotab is designed to dissolve on the tongue whereas the orodisperable tablet is designed to dissolve in a liquid and be drank.

[Gibby]

My first taper was conducted with a compounding pharmacy making custom capsules. I made a mistake in making it a ten percent reduction from the ORIGINAL dose rather than from the current dose each time, so it went too fast and when I got down to about 1.5mg things got a little hairy.

 

I'm planning a new taper that will be MUCH longer. I know I'm sensitive enough that the long way is probably the only way. 

[simack]

Hey all, I was looking for a bit of help switching from tablet form olanzapine, to a liquid suspension form made from orodisperable tablets. I tried switching over on the weekend, and ran into trouble with insomnia on the second night. My current dose is 3.75mg tablet form, so I mixed a 5 mg orodisperable tablet into 20ml of water, then cut 5ml out, hopefully giving me 3.75mg liquid form. This didn't seem to work for me should I try increasing the dose slightly to say 4mg and see if that works?

[erer]

Hey all, I was looking for a bit of help switching from tablet form olanzapine, to a liquid suspension form made from orodisperable tablets. I tried switching over on the weekend, and ran into trouble with insomnia on the second night. My current dose is 3.75mg tablet form, so I mixed a 5 mg orodisperable tablet into 20ml of water, then cut 5ml out, hopefully giving me 3.75mg liquid form. This didn't seem to work for me should I try increasing the dose slightly to say 4mg and see if that works?

 

It seems you did everything correctly. Could it be that it is the change from the regular pills to the orodispersible ones that is doing this? Because there are different additives in the pills. It could be like it is when changing from one brand name to another.