Increased amt of cyclosporine-side effects?

[jenny2008]

Hi,

I am tempted to try the increased amt of cyclosporine that a few people on here have spoken about .... I spoke with my doctor in Louisville and he said he would prescribe it for me but warned that the vehicle it comes in-corn, olive or peanut oil could disrupt my tear film and I may not be able to tolerate it. I am one of those people who cannot tolerate BAK or any other ointments and drops. I have to used the non-preserved type of Steriods from Leiters as Lotemax has BAK in it and disrupts my tear film. I couldn't tolerate Azasite either---I am tempted to try the higher dose but am scared it could hurt me..

Has anyone tried the higher concentration and had problems with the oil it is in even though it isn't a preservative???? I appreaciate any thoughts on this!
Thanks..
jen

[pecan121]

I wanted to do the same thing and yesterday my doctor was receptive to the idea but wanted to check with some colleages first. Today he told me that the other doctors were okay with Restasis 4 times a day or compounded cyclosporine at the same strength, but had concerns about a stronger dosage because of damaging the eye. I am really disappointed because I have seen an improvement in the short time I have used it 4 times a day, but I wanted the convenience of two times a day. Restasis 2 times a day seemed to do nothing.

Like you I am interested in hearing other people's experiences.

[jenny2008]

My doc said i could try but am so worried about my tear film and getting worse... if anyone out there has gotten worse from it please post it!

[willwork4tears]

Hey guys,

I've been doing a lot of research on this because there is really conflicting evidence out there. I found out through a PM that another DEZ poster saw a bigwig corneal specialist who wouldn't write a script for higher dose cyclosporine because long term use/high doses are dangerous. He advised her to stop using Restasis completely and cited some research he had done. Yikes...I've been using higher doses for over 8 weeks. Did I miss something? Did my doctor miss something? What if this guy is right?

I talked to my eye doctor again and told him about the other corneal specialist's opinion. My eye dr reiterated that cyclosporine is safe in doses up to 2% (and perhaps higher) and cited some research that he had done.

Here's the crazy thing. My eye doctor did his fellowship with the other eye doctor and they were citing THE SAME RESEARCH! Confused? Yeah...My eye doctor was really confused, too! He just frowned and said he didn't know why his former mentor/advisor would be telling people Restasis isn't safe. So who do I believe when 2 corneal specialists give conflicting advice on the same research??? When in doubt check the literature.

I found studies showing that cyclosporine isn't toxic at doses even beyond 10%. So what causes the toxicity? The vehicle. Alcohol causes toxicity problems. Also, castor oil caused significantly more toxicity problems than corn oil. I found all this really interesting. So THEY'RE BOTH RIGHT. Cyclosporine isn't toxic and Restasis and compounded medications could be bad for you. It depends on how much alcohol is in there, what the diluting oil is, are there preservatives, etc.

I will post the article tomorrow. I have it saved on my hard drive at work...I had to translate it from french, so I'll post the original article and the translation and you guys can see the study, print it out and take it to your doctors! Then you and your doctor can use peer-reviewed ACTUAL INFORMATION to make an informed decision on what is best for your eyes. Yeah! This is why we're on the DEZ, right? High quality information.

Don't trust doctors that make anecdotal assumptions. Ask them to back up their opinion with facts. They may be "right" but the interpretation is all in the details.

[jenny2008]

You are great! i look forward to the article!! this board needed someone like you!

[willwork4tears]

Why thank you! Glad I can be of service! I'm going to make you wait with baited-breath ON for the French research article ....but in the meantime you can lull yourself to sleep with a little late night read of this review article. Table III summarizes the research done in humans - most of them using 2% cyclo in some kind of oil. It gives the reference for each study in the rightmost column.

http://dl.dropbox.com/u/4805513/cycl...y%20review.pdf

[Rebecca Petris]

Excellent - thanks much for the link. Interesting paper. I haven't really been keeping up with the cyclosporine issues much so this was very helpful.

I found it interesting that while...

No quantifiable ciclosporin was detected in the blood of any patient receiving ophthalmic 0.05% ciclosporin emulsion in both eyes twice daily for up to 1 year.

(i.e. Restasis at standard approved dosing) ...but this was not always true at higher concentrations, and higher frequencies of the lower (0.05%) concentrations were not studied.

So I wonder if this is one of the things some doctors are questioning as high-frequency dosing of Restasis is on the increase and more and more patients are getting higher concentrations compounded. I will have to bone up on this.

The two pipeline drugs most likely to next be approved are both cyclosporine. Zyclorin is 0.1% and I don't know what Cyclokat is. At any rate we should be seeing some more interesting data before long as well.

By the way... I think there are a lot of perfectly legitimate reasons why doctors will conclude different things from the same study... and quite possibly different things than the 'conclusions' of the study. At the end of the day a study is a selectively presented interpretation of a selection of data. The raw data can be sliced and diced in so many ways.

[Pinky]

Willwork4tears,
Thanks for the info.

Do you know if a gum cellulose base has been found to cause toxicity? Leiter's Pharmacy offers this as an alternative to those who can't tolerate any of the oil vehicles. I have a friend with DES who has been unable to tolerate olive oil or castor oil, but has had success with gum cellulose.

[jlg_uk]

Interesting timing of this thread. Following an appointment with my Ophth yesterday, I was prescribed Cyclosporine at 2% (Restasis isn't available in the UK).

I expressed some concern at the time as I knew many people can't tolerate it. However, I'm pretty far down the road of things to try so I agreed. I'm supposed to have one drop in both eyes twice per day.

I tried it last night. Installation into the eye was better than I expected (I was expecting instant pain). But over the course of the next 15 minutes it really started to sting/burn and my eyes went red (normally they don't, it's my inner eye lids which go red).

This morning my eyes are fine.

There's no way I could put these in in the morning, but I am considering trying this for a week an hour before bed time to see if there is any improvement both overall, and simply the installation/reaction part. It's hard to know if the reaction is simply due to the carrier fluid and whether the cyclosporine element may help.

[irish eyes]

Hi Jlg

Was it Cyclosporine drops? I tried Optimmune ointment last year and it was horrendous so I had to stop. I think that petrolatum was the main culprit but it might have been the corn oil.

Like you, I was `pretty far down the road' so I was quite happy to give it a go.

I hope you have better luck with it.

[jlg_uk]

Hi Jlg

Was it Cyclosporine drops? I tried Optimmune ointment last year and it was horrendous so I had to stop. I think that petrolatum was the main culprit but it might have been the corn oil.

Like you, I was `pretty far down the road' so I was quite happy to give it a go.

I hope you have better luck with it.

Yes drops - I think tonight I might just try some on my skin (back of hand) - I'll be interested to see if even there I react!

[willwork4tears]

Following an appointment with my Ophth yesterday, I was prescribed Cyclosporine at 2% (Restasis isn't available in the UK). I expressed some concern at the time as I knew many people can't tolerate it. However, I'm pretty far down the road of things to try so I agreed. I'm supposed to have one drop in both eyes twice per day. It's hard to know if the reaction is simply due to the carrier fluid and whether the cyclosporine element may help.

jlg_uk: It's probably the cyclosporine causing the stinging/burning. I started on 1% and my eyes stung/burned terribly upon instillation and also throughout the day for no reason. I switched to 0.2% (also in corn oil) and the stinging/burning went away completely. It is also possible you are sensitive to the alcohol (I may have been as well). Find out exactly how they make it and what else is in there (alcohol, preservatives, dyes). They are probably diluting the liquid concentrate from Sandimmun capsules which contain 12.7% alcohol. So the higher the cyclosporine the higher the alcohol.

I recently moved up from 0.2% to 0.4% and I'm having very little stinging/burning.

I would recommend titrating up slowly from another dose if you're having problems. This worked for me and I know Ringo did this as well and is currently using 2%.

Do you know if a gum cellulose base has been found to cause toxicity? Leiter's Pharmacy offers this as an alternative to those who can't tolerate any of the oil vehicles. I have a friend with DES who has been unable to tolerate olive oil or castor oil, but has had success with gum cellulose.

Pinky, I have no idea, but I would be happy to look into for you and let you know what I find in a couple days.

By the way... I think there are a lot of perfectly legitimate reasons why doctors will conclude different things from the same study... and quite possibly different things than the 'conclusions' of the study. At the end of the day a study is a selectively presented interpretation of a selection of data. The raw data can be sliced and diced in so many ways.

Rebecca: I completely agree. You explained it brilliantly. The "other" doctor is a bigwig in the field and wouldn't have that reputation if he wasn't a good dr. Also, I trust the judgement of my Dr completely. So I knew there had to be a perfectly good explanation other than simply concluding one of them was "wrong."

[jenny2008]

I put in a call to Dr.Foulks and am waiting for a call back today--I have decided to give it a try... I am going to ask for the corn base since Willworkfortears seems to tolerate it.. (thank you again)... My doc isn't in today but I left a detailed msg and am anxiously awaiting his call.. My eyes got so red and hurt so bad at work yesterday I have to try something.

Worst case scenario it burns/ hurts/ or disrupts my tear film.. I have been through this before and eventually my eyes get back to their 'normal' for sjogrens. If I don't try I won't know..

I will keep everybody posted...

[willwork4tears]

Research on the safety of cyclosporine and vehicles in compounded eye drops

Here's the French study. I'll summarize the parts I found to be helpful.

Figure 1. Rabbit corneal cells were cultured in a plate in the presence of different concentrations of cyclo for 30 min. They they did a test to determine the % of cells that were still alive (% viability). There wasn't a statistically significant decrease in cell viability until the 7.5% dose. Even at 12.5% only 10% of the cells had died. Plus if you put this into the context of eye drops, the drops aren't going to be saturating your eyes for 30 min straight. You'll blink, they'll get diluted with tears, seep out, etc. After 5-10 min most of the medication is either absorbed or blinked out.

Figure 2: Comparing different formulations to assess the role of the vehicle.
B: 2% cyclo, 0.2% alcohol in corn oil.
C: 2% cyclo, 0.2% alcohol in castor oil.
D: 2% cyclo, 2.5% alcohol in castor oil.

Rabbit corneal cells were cultured in a plate in the presence of 2% cyclo in different vehicles for 30, 60 or 240 min.
At 30 min, only formula D showed a significant decrease in cell viability compared to control (plain corn oil). After 60 min, only the drops in castor oil caused a sig decrease in cell viability. After 240, all formulations resulted in decreased viability, but B performed the best.

My conclusion? Keep the alcohol to a minimum, and corn oil is preferable to castor oil. Also, keep in mind that castor oil is EXTREMELY viscous and if you put it in your eyes they'll be blurry for more than 30 min. The corn oil blurs my vision for ~5 min.

http://dl.dropbox.com/u/4805513/Cyto...evaluation.pdf
http://dl.dropbox.com/u/4805513/Cyto...ranslation.doc

[jlg_uk]

jlg_uk: It's probably the cyclosporine causing the stinging/burning. I started on 1% and my eyes stung/burned terribly upon instillation and also throughout the day for no reason. I switched to 0.2% (also in corn oil) and the stinging/burning went away completely. It is also possible you are sensitive to the alcohol (I may have been as well). Find out exactly how they make it and what else is in there (alcohol, preservatives, dyes). They are probably diluting the liquid concentrate from Sandimmun capsules which contain 12.7% alcohol. So the higher the cyclosporine the higher the alcohol.

I recently moved up from 0.2% to 0.4% and I'm having very little stinging/burning.

I would recommend titrating up slowly from another dose if you're having problems. This worked for me and I know Ringo did this as well and is currently using 2%

Unfortunately here in the UK only 2% is available. Also it's an unlicensed medicine and doesn't come with an information sheet - so not really sure what's in it - though I do know it's PF.

Ideally I'd start with Restasis like 0.05% and go from there, but that's not really an option.