ASHP Guidelines on Pharmacy-Prepared Ophthalmic Products
To ophthalmologists: written below is the link for the ASHP Guidelines on Pharmacy-Prepared Ophthalmic Products. ASHP stands for the American Society of Health-System Pharmacists (formerly the American Society of Hospital Pharmacists) . We thank Dr. Sarah Sellers, PharmD, MPH. for providing this link. It might be wise to check that whoever provides you with Avastin or any other drug follows these guidelines. ----- http://www.ashp.org/bestpractices/drugdistribution/Prep_Gdl_Ophthal.pdf
Update from the 29th Annual Meeting of the Macula Society
Most of the world’s experts in macular disease belong to The Macula Society. We just had our annual meeting in North San Diego. I thought it was an excellent meeting and here are some of the highlights:
Lucentis®
The trials involving Lucentis® continue to show excellent results that are much better than treatment with either Visudyne® (PDT), or Macugen®. A re-analysis of the data from the MARINA Study, which compared treatment with Lucentis® to a sham treatment, revealed that Lucentis® was very effective for the treatment of wet AMD no matter what the age of the patient, the size of the new blood vessels, the type of new blood vessels, or the initial visual acuity.
Results from the ANCHOR Study showed that the visual acuity was significantly better in the groups of patients treated with Lucentis® compared to the group treated with Visudyne®. The neovascular membranes continued to enlarge in the Visudyne® (PDT) group during the first year of treatment whereas they pretty much stayed the same size in the Lucentis® group.
Avastin®
Avastin® is the parent molecule of Lucentis®. Since Lucentis® is not yet FDA approved, many retinal specialists are injecting Avastin® into the eye instead. There were four papers on the use of intravitreal Avastin®. All four had very positive results which appeared similar to those with Lucentis® although these patients have been followed for only three to six months. The only ocular complication in the total of 570 patients in these four reports was mild inflammation in the vitreous in three patients which cleared on its own.
So What Now?
This may be controversial, but I’m not going to treat any new patient with Macugen®. I’ll use Avastin® instead or ask the patient if he or she would be interested in participating in a clinical trial testing Lucentis®. If my mother were alive and had wet AMD, I’d tell her the same thing. I asked five or six colleagues at the meeting and they agreed with me although two of them had not yet totally given up on Macugen®. If a follow-up patient appears to be doing well with Macugen®, I’ll continue to inject them with that drug. If they aren’t doing well, (the vision is worse, there’s still fluid in the retina or the neovascularization is growing), then I’ll switch to Avastin®.
Coming up later this week:
Safety of Avastin® and Lucentis®
Challenges ahead
More on AMD from the Macular Society Meeting
And again, my family and I have no stock in the companies that make Visudyne®, Macugen®, and Avastin® and Lucentis® nor am I paid by any of these companies. Please e-mail with any questions.
Thanks,
JCF
Reader Question: Treatment of Second Eye
The following question (paraphrased for brevity) came to me:
After about 18 months of Visudyne treatments (w/o great results), my 77 y.o. mother switched to intraocular Avastin at the end of December 2005. To date she's had 2 treatments (28 Dec & 25 Jan) and on 11 Feb she began reporting little, daily improvements in vision -- can see shredded carrots in her soup and low & behold, her toothpaste has stripes! As refractory as she'd been to the Visudyne (w/o Kenalog), I’ve been delighted with stabilization. The rest is icing on the cake.
The next treatment & full exam are 08 March. It would be useful to know if or how to discuss management of the inactive eye at that time.
Thanks for your balanced & insightful postings on this topic.
Response: Retinal specialists don’t yet know for sure how many treatments of Avastin are enough. We usually give another injection if any of the following are present:
The patient returns with worse vision
The area of the neovascularization is larger.
The patient still has fluid within or under the retina
The patient has subretinal hemorrhage. Hemorrhage is a bit trickier however, because it takes a long time to go away. Therefore hemorrhage can still be present even after the neovascularization has become inactive.
The neovascularization leaks on a fluorescein angiogram.
Fluid within or under the retina is seen with optic coherence tomography.
A fluorescein angiogram involves the injection of a into an arm vein. The dye circulates up to the eye and then photographs using special filters are taken of the area of neovascularization. If the neovascularization has grown in area or is still leaking, that usually means it’s active and another injection should be given.
Optic coherence tomography uses a low-powered laser beam to take cross-sectional pictures of the retina. Fluid within or under the retina is seen as a dark space. The doctor usually gives another injection if he or she sees fluid on the OCT. Sometimes a small pocket of fluid may remain in the retina despite further treatments.
We used to believe that neovascular membranes grew and leaked, then scarred up and remained inactive forever. The careful long-term follow-up of patients within the Macular Photocoagulation Studies revealed however that the neovascularization can reactivate later. Therefore, even patients with “inactive” scars need to be followed and told to return if they develop new symptoms of decreased vision or distorted vision.
To answer the present question: I would not try Avastin if the vision in the inactive eye was lost more than a year ago. I would also ask your mother’s doctor whether there is leakage on the fluorescein angiogram or fluid on the OCT. If either were present, I might try an injection even if there was some scar tissue under the retina. The vision probably won’t improve much but anything helps.
Conversely, if neither leakage nor fluid were present, I would just follow the eye. I would also take your mother to someone for visual rehabilitation, (a low vision appointment), so she can learn to make the most of her remaining vision. Thanks. JCF
Avastin Safety
Earlier this week, the Washington Post and other papers reported that Genentech temporarily halted recruitment into a study testing Avastin® combined with two types of chemotherapy for the treatment of metastatic colon cancer. The recruitment was halted because four patients in one arm of the study died suddenly. One of our blog readers wrote to ask if this means that Avastin® could be dangerous to his father who was being treated with the drug for AMD.
The sudden deaths were only among patients in one arm of the study. Another large group of patients who were also taking Avastin® (with a different type of chemotherapy) didn’t show this increased risk. Overall, there were relatively few deaths in the 2000 patients in the study. Therefore there is a good chance that the deaths were not due to Avastin®. Genentech was just being extra careful. The main thing to remember however, is that patients who have colon cancer are treated with intravenous Avastin® at a dose of 5mg per kilogram of body weight. A 154 pound person weighs about 70 kilograms which means that person would receive 350 milligrams of Avastin® intravenously every two weeks. The dose we use for AMD is 1.25 mg (280 times less) given every four weeks. So our dose is 560 times less per month. The Avastin® is also placed into the eye so it would first have to leak out of the eye and into the bloodstream to cause systemic complications. Therefore I believe that a systemic complication from the Avastin treatment that we use in AMD would have to be exceedingly rare. Another article ( PMID: 16458968) that will be published by Dr. Robert Avery and colleagues in the March Ophthalmology issue states that Avastin® was found to be safe and effective in the treatment of 79 patients with AMD. The patients, at the time the article was written, had only been followed for about two months so we don’t know what the long-term outcome will be. The early results look encouraging however and any side-effects should have occurred within a week or two after the injection. In summary, right now, Avastin® looks to be both effective and safe for the treatment of wet AMD. We do need to follow more patients for longer periods of time though to be absolutely sure. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal Bevacizumab (Avastin) for Neovascular Age-Related MacularDegeneration.Ophthalmology. 2006 Feb 1; [Epub ahead of print] PMID: 16458968
Reader Question: Avastin vs Lucentis
A reader asks: “From what you've observed in using Avastin® and from the reports from Lucentis® trials are you seeing marked differences in the results of the two products? Perhaps Dr. Folk would comment in his blog. Also, when would one use a "deadener" in the eye as opposed to a topical before the Avastin injection?”
My answer: Retinal experts have not followed patients who have had Avastin® long enough to determine whether or not the results are similar to Lucentis®. The early results with Avastin have been very good however, so my feeling is that they will be similar to those with Lucentis®. I have used cotton swabs wet with topical 4% Lidocaine alone to numb the area of injection. About one-third of these patients will feel some pain with the injection. I haven't used Lidocaine® gel to numb the area but would think that the percentage would drop. I still raise a small subconjunctival bleb of Lidocaine® in most patients in the area of injection. If you wait at least three minutes, only about 10% of these patients will feel anything when the Avastin® is injected. Most of these patients however will have some subconjunctival bleeding after the Lidocaine injection which is harmless but can look bad. I tend to use topical Lidocaine® only in patients who are on aspirin or Coumadin® because of the subconjuctival bleeding. -JCF
Treatment Trends for AMD, February, 2006
I promised to keep you up on the number of different treatments for wet AMD that we’re using at The University of Iowa. Here are the number of treatments by month:
| Treatment | September | October | November | December | January |
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Visudyne® | 28 | 19 | 24 | 14 | 18 |
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Macugen® | 25 | 22 | 24 | 25 | 24 |
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Avastin® | 2 | 21 | 38 | 42 | 53 |
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 The number of Visudyne treatments is decreasing. Visudyne is pretty much used now only for small classic CNV. Occasionally Visudyne is used for large classic CNV but only in patients who have already lost vision, because I think that it causes more scarring than Avastin. Macugen can be used for all types of CNV and the number of treatments is holding steady. I don’t know how many of these treatments were on new patients and how many were repeat treatments on return patients. The main trend is that the number of Avastin treatments is increasing. I believe the reasons for this increase are: My colleagues and I have not seen any side-effects with Avastin so we’re getting very comfortable using it.
Avastin seems to “dry up” neovascularization promptly. In other words, it works and it works quickly.
We are treating patients with small occult CNV earlier. Before we were more likely to watch these patients until the CNV grew or the vision decreased because we were worried about the side-effects of treatment. Macugen doesn’t promptly stop the leakage of these patients. Visudyne (with Kenalog in these patients) also seems to work but sometimes the membranes grow and bleed.
Avastin is being used in patients with large CNV with leakage and poor vision who have failed other treatments. Before we tended to “give up” on these patients believing that nothing further would help. Avastin gets rid of the subretinal fluid and there is a modest return of vision which most patients notice and appreciate.
We’re gaining more knowledge about Avastin and Lucentis almost on an daily basis. There are surveys being done to determine if any retinal expert has seen complications from Avastin. In the next few months, as we follow patients, we’ll get some idea as to how many injections of Avastin are needed to control the neovascularization. Currently I usually give three injections at 4-6 week intervals. If the neovascularization is controlled (same size, no leakage) and the OCT shows no fluid or just one or two small cysts in the retina, then I just watch. We’ll see how many of these patients develop recurrent symptoms and how many are stable. Good luck!
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