Protopic 0.1% Ointment Tacrolimus Monohydrate

[Brighteyes]

Has anyone heard of Protopic 0.1% Ointment Tacrolimus Monohydrate (a.k.a. Topical FK 506 Ointment 0.1%)? Supposedly its a new therapeutic option for atopic blepharitis. Here's a short blurb about the study:

Mayer K, Reinhard T, Reis A, Böhringer D, Sundmacher R.
Augenklinik, Heinrich-Heine-Universität, Düsseldorf.
BACKGROUND: Severe atopic blepharitis is difficult to treat, as topical steroids offer only a limited therapeutic benefit with increasing side effects by time. Topical FK 506 was found to be efficient and safe for treatment of atopic dermatitis in dermatologic studies. The use of topical FK 506 in atopic blepharitis has not been reported so far.
PATIENTS AND METHODS: Fourteen patients with severe atopic blepharitis were treated with topical FK 506 0.1 %. The ointment was applied twice daily on the eye lids. Ophthalmologic examinations were scheduled at two weeks, two months and five months after onset of treatment. A score was defined for the skin of the lid (edema, erythema, lichenification, oozing, excoriation and crusting) and for the eye lid margin (erythema, thickening, crusting) respectively. Every patient graded pruritus on a visual analogue scale.
RESULTS: The mean skin score prior to treatment was 25.6 +/- 5.8, after two weeks 7.9 +/- 4.8 (p < 0.001), after two months 5.8 +/- 5.0 (p < 0.001) and after five months 5.3 +/- 5.3 (p < 0.001). The mean score for the eye lid margin prior to treatment was 12.3 +/- 4.0, after two weeks 4.6 +/- 2.7 (p < 0.001), after two months 3.8 +/- 2.4 (p < 0.001) and after five months 4.3 +/- 2.6 (p < 0.001). The mean score for pruritus prior to treatment was 8.1 +/- 1.3, after two weeks 2.0 +/- 1.4 (p < 0.001), after two months 1.3 +/- 0.8 (p < 0.001) and after five months 0.8 +/- 0.7 (p < 0.001). All patients assessed the overall situation under therapy as markedly improved.
CONCLUSIONS: Topical FK 506 0.1 % ointment turns out to be an excellent therapeutic option for treatment of severe atopic blepharitis. Long-term efficacy and safety have to be evaluated in long-term follow-up studies.

To find more info search "fk506 treatment for blepharitis" @ http://www.ncbi.nlm.nih.gov/sites/entrez

[Kathel]

Yes, Protopic ointment has been available (prescription) in the US for about 5 years now. I may try it myself. Thanks for the post.

Kathel

[Scout]

Please see this thread in the archives:
http://www.dryeyezone.com/talk/showt...ght=tacrolimus

Tacrolimus has been found in rare cases to cause cancer, particularly in children.
http://www.rxlist.com/cgi/generic/tacrolimus_wcp.htm

WARNING

Long-term Safety of Topical Calcineurin Inhibitors Has Not Been Established

Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including PROTOPIC Ointment.

Therefore:

· Continuous long-term use of topical calcineurin inhibitors, including PROTOPIC Ointment, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis.

· PROTOPIC Ointment is not indicated for use in children less than 2 years of age. Only 0.03% PROTOPIC Ointment is indicated for use in children 2-15 years of age.

Prolonged systemic use of calcineurin inhibitors for sustained immunosuppression in animal studies and transplant patients following systemic administration has been associated with an increased risk of infections, lymphomas, and skin malignancies. These risks are associated with the intensity and duration of immunosuppression.

Based on the information above and the mechanism of action, there is a concern about potential risk with the use of topical calcineurin inhibitors, including PROTOPIC Ointment. While a causal relationship has not been established, rare cases of skin malignancy and lymphoma have been reported in patients treated with topical calcineurin inhibitors, including PROTOPIC Ointment. Therefore:

· PROTOPIC Ointment should not be used in immunocompromised adults and children.

· If signs and symptoms of atopic dermatitis do not improve within 6 weeks, patients should be re-examined by their healthcare provider and their diagnosis be confirmed (see PRECAUTIONS: General).

· The safety of PROTOPIC Ointment has not been established beyond one year of non-continuous use.

From the FDA website:
http://www.fda.gov/cder/drug/advisor...l_protopic.htm

Elidel cream and Protopic ointment are topical immunosuppressant calcineurin inhibitors that are applied to the skin and are the only approved drug products in this class.

Animal studies have shown that three different species of animals developed cancer following exposure to these drugs applied topically or given by mouth, including mice, rats and a recent study of monkeys. These studies were conducted at doses higher than generally used by patients and the risk of cancer increased with increasing drug dose and duration.

In addition to an ointment, tacrolimus, also comes as a pill or by injection, this form is known as (Prograf). Prograf is approved to prevent liver or kidney transplant rejection. It is known to cause both skin cancers and lymphoma in humans by suppressing the body’s normal immune defenses against cancer. The cancer risk increases with higher doses and longer treatment courses of Prograf. Both Elidel and Protopic are sometimes absorbed through the skin, though usually at very low amounts. Occasionally, children who have been treated with Elidel or Protopic have had high blood levels of these drugs.

Protopic was approved in December 2000 and Elidel in December 2001. Since their approval, FDA has received reports of lymphoma and skin cancer in children and adults treated with Elidel or Protopic; whether the reported cancers are associated with these products has not been clearly established.

Based on the advice of the FDA Pediatric Advisory Committee, which met on February 15, 2005, to review these findings, FDA will require labeling changes for Elidel and Protopic, including the placement of a boxed warning about the potential cancer risk. In addition, FDA will work with the commercial sponsors of the drugs to develop and implement a Medication Guide (MedGuide) to provide this information and instructions about appropriate use of Elidel and Protopic to patients, their families, and caregivers. MedGuides are intended to be distributed by pharmacists with each prescription or refill of a medication.

This is all regarding the topical skin treatment for atopic dermatitis. As the archived thread indicated, the original pharmaceutical company marketing the opthalmic medication voluntarily removed it.

I think there are still studies being done for an ophthalmic medication, but as far as I know, none are available in the US right now. Anyone else know?

Scout

[Brighteyes]

I'm gonna give protopic a try. I talked to someone on blepharitis support forum who said protopic worked wonders for his condition - so much so that it's not really a problem anymore. His bleph was due to seb derm and my bleph is due to either rosacea or atopic derm so we'll see. I'll update in a few weeks.

Btw this person explained that he used only the smallest amount possible and applied it to the lid and lid margin although not past the eyelashes (not inside the eyelashes) and only every few days.

[sazy123]

Whats 'atopic bletheritis'? all these different names for bleptheritis.. its confusing.

[Brighteyes]

Sazy, I believe the term "atopic blepharitis" refers to blepharitis caused by atopic dermatitis. I could be wrong - it's been known to happen .

Anyways, despite the cancer concerns I decided to give Protopic a try last night. I applied a very small amount (using q-tip aka cotton bud) to my lid margin - but was careful not to apply past (inside) the eyelashes. From talking to people on other forums who've had good success with this treatment I was told to expect burning and redness for about a day (which is exactly what's happening at the moment) but that you only need to apply it every few days and that it should help relieve the symptoms. Will keep everyone updated with my results.

[sazy123]

Sazy, I believe the term "atopic blepharitis" refers to blepharitis caused by atopic dermatitis. I could be wrong - it's been known to happen .

Anyways, despite the cancer concerns I decided to give Protopic a try last night. I applied a very small amount (using q-tip aka cotton bud) to my lid margin - but was careful not to apply past (inside) the eyelashes. From talking to people on other forums who've had good success with this treatment I was told to expect burning and redness for about a day (which is exactly what's happening at the moment) but that you only need to apply it every few days and that it should help relieve the symptoms. Will keep everyone updated with my results.

Thankyou

How would one know if they had atopic dermatitis? what is the appearance of this as ecxma? or does dry skin/dandruff equate to this as well.
uff and dry skin (face) may be causing the eye problem.

[jlg_uk]

Despite it's flaws, I like wiki.

http://en.wikipedia.org/wiki/Atopic_dermatitis

[sazy123]

Brighteyes do you have an update?

Im going to try this despite cancer risks, my eyes are bad enough to warrent the risk. But i will only use abit and be very careful to apply with shut eyes and not to get in the eyes.

[Brighteyes]

Hey sazy - its going ok so far - I've only applied it three times. My eyes were really red and burning/hot after the first application (think I got it in my eyes) so I didn't apply it for 5 days afterwards. But three days afterwards my eyes were great - I didn't even put in visine when I went out last weekend. I have applied it twice since (2 days in a row) and was careful not to get it in my eyes - its really a fine line since you want to apply it to the lid margin but you don't want to get it in your eyes. One trick I found is don't put eyedrops in after you apply the protopic because it will spread it to your eyes. I've been waiting at least 15 minutes after eyedrops to apply the protopic (at night) and then do lid cleanses in the morning before using eyedrops. Hope this helps.

I'm going to post future updates on the protopic log instead of this thread.

[sazy123]

thanks brighteyes, i read on here (did a search) someone was prescribed the drop version (which was under study for dry eye) but they cancelled it due to risks with the cream. I wondered how would one be prescribed these if it was investigational? Leiters maybe?

The immunosepressant inflammatory action of this makes sense for me because my dry eye is caused by immune modulated inflammation, which goes away when im ill and my eyes are so much better- in this instance the immune system is not creating inflammation at eye site because its otherwise engaged. However steroids never helped and they are supposed to suppress the immune system response where topically applied.

[Brighteyes]

Sazy - What is "immune modulated inflammation"? Auto-immune? Have you looked into an underlying auto-immune disease being the cause of your dry eye? I'm just realizing that I might have rheumatoid arthritis - which would explain all my current symtoms - dry-eye and other.

[sazy123]

Hi yeah i mean auto immune inflammation, but not necessarly, inflammation comes from the immune system- its way of repairing something, if theres a chronic problem it will keep sending inflammation but it cant fix the problem (not sure if its the same thing). Anyway no i dont have underlying auoto immune conditions, ive been tested for sjgrens and other problems blood tests came back negative. I dont have any other sysmptoms when my eyes are bad and ive always been healthy. I do get fibro type pain in the past- but this is a result of extreme stress of living with dry eye- i dont have dry eye when i have this becuase the inflammation clears up, same with any other illness.

The only thing i deffinately have is rosacea (but mild), and on and around my eyes there is some faint redness similar to that on my face. Roscea causes autoimmune inflammation. I just think my eyelids have vascular damage from contact lenses and thats why nothing helps, nothing touches this inflammation either.


I looked at your past posts, do you still think you have ocular rosacea or more likely excema (atopic bleth)? causing MGD.

[sazy123]

I found this article (recent) which claims dry eye is autoimmune

http://dryeyedigest.blogspot.com/200...e-dry-eye.html

[Brighteyes]

Sazy - Autoimmune diseases cause your body to attack itself - thinking your body is an invader - inflammation is your body's response to invadors. I have some unknown underlying condition that is causing my dry eye symptoms. At the moment I think it's rheumatoid arthritis (still waiting for test results). Here's a quick timeline of my symptoms:

June 2003 - conjunctivitis and chalazon in right eye (went away)
October 2006 - dry eye symptoms right eye
January 2007 - dry eye symptoms both eyes
June 2007 - left elbow contusion - bursitis - recurring elbow pain
October 2007 - left knee contusion - recurring knee pain
January 2008 - rosacea symptoms
June 2008 - numbness in ring and pinky fingers (after leaning on elbows)
January 2009 - joint discomfort

As you can see, I've experienced a worsening of symptoms over the past two years which causes my diagnosis to be ever changing. At the moment I think it's rhuematoid arthritis - which would explain dry-eye and rosacea-like symptoms.