Benzalkoinium Chloride Damage

[Guest]

kakinda

It seems that this company produces a lot of PF drugs here in the UK.

I will try and get you an inner leaflet.

As far as prescription cost goes, in the UK it is £6.65 for an NHS prescription per item. Usually an item is a months supply, for example my GP prescribes me Minims Saline PF in single use vials (they come in a box of 20) but because I use them 2-3 a day, I get 3 boxes on my prescription for £6.65.

I will ask my pharmacy tomorrow but I would imagine that NHS prescriptions would be limited to UK residents for obvious reasons. They may however, dispense it as a private prescription (on your french prescription) where you then pay the actual drug cost.

Maybe you could make direct contact with the company or have your doctor contact them to check about availability.

Cheers

Ian

[kakinda]

Thanks Ian,

yes, the minims brand is a group of rather old drugs but in PF versions... at least they safe BAK-wise although they may produce more side-effects that new and milder steroids in the case of prednisolone... If by any chance you came across a complete list of the minims series could you please send it to me....

If you can please ask what the actual cost is?

It is historically a French lab (Montpellier) so I'm going to contact them about getting minims here... just need to find some time to do that.

thanks again,
Take care

[np1981]

....my GP prescribes me Minims Saline PF in single use vials (they come in a box of 20) but because I use them 2-3 a day, I get 3 boxes on my prescription for £6.65.

Yeah I get the exact same thing. But I managed to get 4 boxes under one prescription. If I pestered my GP even more, I may be able to get more!

[Guest]

NHS Prescription required

Kakinda,

I asked at my pharmacy on Friday and they said that they could only dispense on a NHS Dr's prescription from a UK Dr.

I asked about a private prescription and they said it wasn't possible.

I am very new to this NHS prescription stuff myself, maybe someone else can offer some assistance.

I don't have the insert either, if someone else has a copy maybe they could forward it through to you.

Sorry I can't be more assistance.

Ian

[SusieD]

Hi

Ive also used the Minims prednisolone - the first prescription I had was a private one and I paid around £20+ for one boox/20 vials - so not exactly cheap. Further prescriptions were NHS ones.

They also do Dexamethasone but these are even stronger than the pred. Its a shame they dont do FML as a pres free, its not as mild as the lotemax etc but at least its milder than the prednisolone.

Minims also produce:

Antibiotics:
Chloramphenicol (a doc at the hospital where I worked gave me some for an eye infection - this ones kept on all wards in the fridge - broad spectrum).
Neomycin

Artificial tears and saline.

Range of glaucoma meds in single use vials - sorry can't find an inclusive list.

Range of drops used to aid in the examination of eyes including, flourosceine (sp?) rose bengal, and other drops used in eye exams, cycoplegic drops etc. The NHS must have a contract with them because you go to any ophthalmologist here and you'll see the trademark blue and white boxes scattered around the office.

Back to the steroids - Im sure I still have the inserts if you want me to send it just let me know.

[kakinda]

Hi Susie,

yes, Keratos (and myself) would appreaciate having a copy of the insert. It's one alternative for people who can't stand preservatives when there is none currently in France, in spite of many requests by the main French hospitals... and Keratos

I'll send you a private email on Kerato's address...

I hope they will produce a PF version of a milder steroid someday... that would really make sense medically...remember primo non nocere (first do no harm)... or first do less harm should i say (no preservative and less side-effects).

Thanks a lot,
take care
K

[Guest]

Correction!!!!

....my DR put me on a 10 day course of preservative free Prednisolone Sodium Phosphate (0.5%) brand name Minims (Chauvin Pharmaceuticals Ltd Surry KT2 6TN).

It seems I was mistaken the steroid I was on is:
Minims 0.1% Dexamethasone Sodium Phosphate PhEur (DSP 0.1) and not Minims 0.5% Prednisolone Sodium Phosphate BP (Pred 0.5)

I have no idea what the difference between the two is, nor am I sure how I could make such a mistake in the first place.

Anyway, Minims make two PF steroid drops (as well as the Saline - which I use also).

Sorry if this has caused any confusion.

Ian

[kakinda]

HI again,

Dexamethasone is another type of steroid of course.... so if it's not too much of a bother could you please keep an insert next time for me and send it to Keratos.

dexa... lasts longer so that's why every other day or every third day is usually the posology, I don't think that's the case for prednisolone.
But I would like to learn more about long term side effects and compare it to prednisolone.
I will try to ask that to Baudouin next time. I'm sure this is an important issue for you as well.

But i don't think this is the mild steroid...we are hoping for in PF version.

Take care,
K

[Nikki]

Lotemax

Hi,

in the US, Lotemax is supposed to have much improved safety profile - as it's a ketone instead of ester, or vice versa. In any case, the bad part is that, as like most other steroids and prescriptions, it contains benzalkonium chloride.

Plfugfelder, et al. wrote an article pertaining to the use of Lotemax for dry eye patients with delayed tear clearance - and it is shown to help, but in patients with "delayed tear clearance" - the BAK stays on the surface of the eye longer, thus somewhat negating the positive improvements of the steroid. I have "delayed tear clearance" because of my conjunctivochalasis - so it isn't very helpful to me. I don't know what other conditions would have "delayed tear clearance". I did not have LASIK or any refractive eye surgery.

I checked with my pharmacist to determine if a preservative-free version could be compounded - and the response was that the raw materials are not available on the market, so no, a preservative-free version can not be compounded. Which is really a shame, because a safer steroid would benefit so many dry eye patients, myself included.

So I would guess that the patent for Lotemax would have to run out first in order for a non-preservative version to be available?

If anyone is interested - Leiter's Pharmacy has a number of other ophthalmic compounded solutions - and trehalose is one of them. Trehalose has been shown in studies to prevent dehydration - and Leiter's Rx for Trehalose is preservative-free – If interested in the studies, just do a search on pubmed or medline for trehalose and dry eyes. Don't know how many opthalmologists would be willing to write Rxs for Trehalose, but it may be worth a shot.

I've tried to get my eye doc to hook me up with autologous serum drops, but his response was that it contained IgG, and wouldn't benefit me. I don't know if it would help my condition or not, but do know that the autologous serum is one (of a few possibilities) of an eye drop that would be preservative-free.

Don't know if that helps anyone,

Scott

[kakinda]

Hi

Re Lotemax: no PF version yet... so not really an option for most of us. Unless the pharmas are forced to produce a PF version.

Re trelahose: I don't know what happened to trehalose in commercial terms... i saw fantastic reports a few years ago and then... If you try them please keep us posted.

Re Autologous serum. If you are allergic, then you may have IgE in them as well. It certainly a good option to get growth factors you can't get anywhere else as of late 2006. Certainly an option to heal ulcers, RCE, etc...I just wish they could remove the bad things in it too (such as the inflammatory substances we both mentioned). Once they'll be able to do that, then there will be a lot of future applications for these drops...

Take care
K

[neil0502]

Hi. Johnny One-Note here ... your friendly anti-BAK lunatic.

Here's another pretty intelligible indictment of BAK after clinical studies comparing unpreserved lube drops, lube drops preserved with BAK, and lube drops preserved with chlorobutanol.

[emphasis added]

Benzalkonium chloride is
known to have significant toxic effects on the corneal
epithelium even when compared with other preserva-
tives. Such effects could be demonstrated for the corneal
epithelium of the rabbit in numerous scanning electron
microscopic studies. Even in concentrations
of 0.001% to 0.1% benzalkonium chloride leads to loss
of microvilli, disruption of intercellular connections and
finally even to complete desquamation of the superficial
cell layers.

Benzalkonium chloride affects the diffusion barrier
of the corneal epithelium in two ways: (1) benzalkonium
chloride leads to disruption of the zonulae occludentes,
which seal off the superficial epithelial cells, thereby al-
lowing aqueous substances into the intercellular space
of the epithelium; (2) the benzalkonium chloride mole-
cules are incorporated into the cellular membranes of
the epithelial cells by their lipophilic chains, thus provid-
ing gates for ionic, aqueous substances to penetrate
through the lipophilic membranes into the intraceUular
space. An increase in corneal epithe-
lial permeability due to topically applied benzalkonium
chloride has been demonstrated both in vitro and in
vivo in rabbits, as well as in human subjects.

The benzalkonium chloride molecules are bound onto
the corneal surface immediately after instillation, wher-
eby the preservative escapes rapid washout by the tear
film. Even 9 days after instillation of a single drop
containing 0.01% benzalkonium chloride residues of the
preservative have been detected in the rabbit epithelium
by a radiocarbon technique. The half-time life of
benzalkonium chloride in the corneal epithelium of the
rabbit is about 20 h, so application several times
daily leads to an accumulation of the preservative. Al-
though preservatives seem to damage the corneal epithelium
of rabbits more than human beings, it is conceiv-
able that when benzalkonium chloride is used as a pre-
servative in artificial tears and is applied several times
per day over long periods, it is accumulated in the corne-
al epithelium, thus leading to further destabilization of
the compromised dry corneal surface. In addition, as
benzalkonium chloride is a detergent, it emulsifies the
lipid layer of the tear film, further compromising the
already insufficient tear film in dry eyes.

The noxious effect of benzalkonium chloride as a pre-
servative in artificial tears was demonstrated both objec-
tively and quantitatively in the present clinical study.
In contrast to the other two tear substitutes tested in
this study, artificial tears preserved with benzalkonium
chloride failed to improve the disturbed corneal epitheli-
al barrier function in dry eyes. Preservation of artificial
tears with benzalkonium chloride should therefore be
abandoned.

Original article: http://www.springerlink.com/content/...5/fulltext.pdf

NOTE: I'm going to reach out to the author to see if he'd work with me/some of us to get this preservative out of our eyes....

[Vicki In Oregon]

Been using BAK and didn't even know it.

The local dry eye expert prescribed me Xibrom. I immediately took it because I was trusting the doctor and was desperate. He also diagnosed me with recorring corneal erosion dystrophy which the other doctors had not. Waited months to get an appt. It is an anti inflammatory. My eyes have only worsened since they began in June and the rest of my dry areas as a result of Sjorgens that was just confirmed. So maybe that is why restasis has not worked. Anyway, today I was looking at the Xibrom I have been using twice a day and the 2nd ingredient is benzalkonium chloride. (.05mg/ml). My eyes kill me 24/7 and my vision is messed up. I am sleepy 24/7 no matter how much I sleep. Not sure what part of that is due to my eyes hurting and feeling so tired they just want to be permanently closed versus fatigure from the sjorgens and fighting the pain all the time. Now I wonder what new kind of damage may have been caused with the BAK and the little bit of hydrogen peroxide that got in my eye. Plus, a week ago I accidentally got hydrogen peroxide in my left eye and since then that eye has not been the same despite my flushing it out and using artificial tears so much. I worry I may have caused permanent problems only because I am not starting off with healthy eyes nor healthy immune system to fight it. I am unclear as to waht this serum is and how you get it? And has it helped anyone?

Any advice appreciated. Thank you.

[Rebecca Petris]

I am unclear as to waht this serum is and how you get it? And has it helped anyone?

If you are talking about autologous serum drops you can read about them in this forum and in this listing.

If you have concerns about BAK in a prescription eyedrop that you have been prescribed, you should talk to your doctor about it to better understand the tradeoffs and whether there may be an acceptable alternative.

[neil0502]

Yet another study (feel free to ignore if you're already a "True Believer" )

I do NOT know how long BAK stays in the eye, the punctal plugged eye, the cauterized eye, the contact lens-wearing eye, etc., etc., BUT ... other studies show that the BAK molecule is NOT washed away by tears, so ... it's reasonable to assume that it hangs in there for a long time.

So ... BAK quickly induces evaporative dry eye, too. In't that special? Hmm?

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16688112

[emphasis added]

Impact of short-term exposure of commercial eyedrops preserved with benzalkonium chloride on precorneal mucin.Chung SH, Lee SK, Cristol SM, Lee ES, Lee DW, Seo KY, Kim EK.
Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. sohhyang@hanmail.net

PURPOSE: The aim of this study is to investigate the short-term effects of benzalkonium chloride (BAC), a preservative used in many ophthalmic topical solutions, on precorneal mucin in humans. METHODS: Immortalized human corneal-limbal epithelial (HCLE) cells were exposed to eyedrops containing BAC solutions at 0.0025% and 0.01% concentrations for a period of 15 min. Human corneal epithelium was acquired with consent, as a byproduct of elective excimer photorefractive keratectomy procedures after application of Ocuflox eyedrops (0.3% ofloxacin with 0.0025% BAC) for 1 week before surgery. The relative expression of the MUC1 and MUC16 mucin gene was determined by conventional and real-time reverse transcription-polymerase chain reaction (RT-PCR). Monoclonal antibodies for MUC1 (HMFG-1) and MUC16 (OC125) were used in western blot analysis to detect MUC1 and MUC16. Human corneas exposed to 0.01% BAC solutions were examined by transmission electron microscopy. RESULTS: The expression of MUC1 and MUC16 gene transcripts was not changed after exposure to BAC in HCLE cells and human corneal epithelium. However, MUC1 and MUC16 were reduced after exposure to BAC in HCLE cells and human corneal epithelium. Transmission electron microscopy of the anterior corneal surface revealed fixation of the mucous layer after exposure to 0.01% BAC for 5 or 15 min; prolonged exposure (60 min) to 0.01% BAC destroys the mucous layer. CONCLUSIONS: This study demonstrates that short-term exposure to BAC can alter the precorneal mucin.

[Vicki In Oregon]

Neil this is terrible. I had no idea this ingredient was in there. I didnt think to look because this guy is suppose to be "the dry eye guy" here. I dont get why he would prescribe me this. This is terrible. I have used this a lot and from reading on this forum, people have developed dry eyes, including me, even in as little as 2 weeks from a medication. Now I use this stuff for many weeks with the dry eyes I already have. Why would he prescribe me this!??!? I can no longer wear contacts but wonder if contact lens solutions include this ingredient? Did the use of this preservative cause you decrease in tears or quality tears or both? Since your cauterized eyes are not enough I assume the quality of your tears also. This is incredibly upsetting to me now. Tomorrow I will be getting upper control flow plugs and I fear it will either not be enogh pain relief or else experience blurriness like before.