The American Academy of Ophthalmology is attempting to guide surgeons
through a time when Wydase is in short supply — and will soon be
PHILADELPHIA Surgeons accustomed to using Wydase
(hyaluronidase) to enhance the effect of anesthesia are now facing the fact
that the drug will no longer be available through its manufacturer,
Wyeth-Ayerst, based here.
In January, Wyeth-Ayerst announced it would not resume Wydase
production. The drug has been in limited supply since Wyeth-Ayerst voluntarily
closed its manufacturing facility to address quality assurance issues. The
closure was temporary; the facility is open, but no Wydase is being made. Its
current supply is in controlled inventory and is anticipated to last until
April. Unless another drug manufacturer assumes production, Wydase will then be
Wyeth-Ayerst spokesperson Douglas Petkus said the company was
shutting down production of the drug because Wyeth had re-evaluated its product
portfolio and its priorities and would be moving on to other areas.
Mr. Petkus also said that Wyeth was working with physicians and
the American Academy of Ophthalmology (AAO) to find other solutions for the
Wydase shortage, but that Wyeth still had a supply until April. He said he knew
of no emergency situations that had arisen.
According to Mr. Petkus, the patent protection on Wydase expired
several years ago and any manufacturer who cared to would now have the legal
right make the drug.
A timeline of events
In 1999, the Food and Drug Administration (FDA) inspected the
plant producing Wydase and determined the 70-year old plant required major
updating to bring it into regulatory compliance.
In February 2000, Wyeth-Ayerst voluntarily closed the plant and
stopped manufacture of some products, including Wydase, while it addressed
quality assurance problems. Wyeth-Ayerst placed Wydase in inventory control and
has provided surgeons with supplies that reflect their previous demand
According to the AAO, Wyeth-Ayerst has tried to supply all
existing customers, but it has not supplied any new customers in the past
In July 2000, the FDA and Wyeth-Ayerst entered into a consent
decree to have evaluations performed by a third party and to have a schedule
for addressing all improvements identified by the FDA.
In November 2000, Wyeth-Ayerst advised the AAO that its inventory
of Wydase will be depleted in early 2001, and that it is expected to take from
6 to 24 months to resume production.
The AAO is attempting several solutions to the Wydase dilemma.
These include finding another manufacturer to take over the production;
identifying manufacturers overseas that might wish to begin production in the
United States; and providing information to surgeons for alternatives to the
use of Wydase in ophthalmic anesthesia, such as an increased use of topical
According to the AAO, with the decreased availability of Wydase
some ophthalmologists are turning to local compounding pharmacies to obtain
hyaluronidase as an alternative to Wydase.
The AAO has stated that unlike pharmaceutical manufacturers,
compounding pharmacies do not come under the jurisdiction, scrutiny and
regulation of the FDA when filling physician prescriptions for individual
However, if a compounding pharmacy solicits prescriptions or
fills orders for a drug without a physicians prescription, the pharmacy
is considered to be manufacturing the drug and would fall under the FDA purview
and its manufacturing standards.
The AAO has stressed that it is important for surgeons to
recognize that there are no uniform national standards for the production of
drugs in compounding pharmacies. All pharmacies are regulated by their
individual state pharmacy boards; some allow medications to be shipped from
state to state.
The AAO has also said that there is no definitive way to ensure
the quality of a drug until it is used; however, certain questions can be asked
of the compounding pharmacy.
The AAO suggests, as a conservative measure, that hyaluronidase
be used within 30 days after it is compounded.
While compounding pharmacies may use United States Pharmacopoeia
(USP) grade base materials, the AAO says this is not a guarantee of the quality
of the finished product. Compounding pharmacies may offer a certificate
of analysis, but it may relate only to the USP composition of the basic
chemical powder and have no relevance to the compounding done by the given
The AAO has received no reports of problems with hyaluronidase
sold by compounding pharmacies.
When the AAO received notice in summer 2000 that Wydase would
soon be in short supply, it formed a task force to evaluate the situation and
procure possible solutions for surgeons accustomed to using Wydase. The task
force offers many suggestions and insights in a round table published on the
AAO Web site.
The task force panel consists of Robert J. Cionni, MD; David L.
Guyton, MD; Michael J. Hawes, MD; H. Dunbar Hoskins Jr., MD; Samuel Masket, MD,
chair of the task force; and Kenneth J. Rosenthal, MD.
In the round table, Dr. Hoskins noted that although Wydase is
used most often in cataract surgery, it has applications in many other types of
intraocular surgery as well; thus, many ophthalmic surgeons will be affected by
tis withdrawal from the market. In 1999, Wydase was used in about 750,000
procedures, he said; used in local blocks, it allows the anesthesia to
disseminate better and more rapidly.
Im now using Wydase in a significantly decreased
concentration, Dr. Cionni said. In fact, I have reduced the
concentration of Wydase to about a tenth of what I used before. I still obtain
the desired akinesia but sometimes need to supplement with topical lidocaine or
tetracaine to achieve a better anesthetic effect.
Dr. Hawes said, The absence of Wydase might also influence
the type of block we give. For example, without Wydase I might be more inclined
to use a regional block rather than a local injection in my oculoplastic
surgery practice. Or I might be more likely to consider general
Dr. Rosenthal said it is possible to give an anesthetic block
without any Wydase, although this approach does pose certain problems. For
example, surgeons might choose to use more volume of anesthetic in order to
produce the same distribution effect, but they may get pockets of high
concentration and intensity of the anesthetic.
There also is some debate over whether extraocular muscle palsies
are linked to the injection of anesthetic without the use of Wydase. It
is my belief that the pooling of the drug could cause toxic levels of
anesthetic to the extraocular muscles, Dr. Rosenthal said.
Dr. Cionni said he uses topical Marcaine (bupivacaine HCl,
Abbott) and/or lidocaine in about 85% to 90% of his cataract surgeries. He
usually supplements that with about 0.2 cc of 1% nonpreserved lidocaine
injected into the anterior chamber at the beginning of the procedure.
However, in my experience, not every patient is a good
candidate for topical anesthesia, Dr. Cionni said. Preoperatively,
I examine patients with the indirect ophthalmoscope and hold their lids open
gently. If they can look into the light, and tolerate it well without
squeezing, then theyre good candidates for topical anesthesia. However, I
believe that those patients who dont tolerate this exam well should be
blocked for their comfort and for the surgeon to be able to safely
perform the surgery.
Dr. Masket said that there have been reports of postoperative
double vision following local anesthetic blocks given without Wydase. While
this is not common, he said, it is probably the chief complication that
concerns the task force. Without Wydase, it takes much longer for the
anesthetic to disseminate, and there also is a greater degree of orbital
To get around that complication, Dr. Guyton suggested that
post-surgical strabismus may be avoided by giving the blocks via an alternative
route. A sub-Tenon infusion rather than a retrobulbar or peribulbar injection
provides blocks that can be just as good, he said.
The anesthetic flows around the back of the globe,
diffusing into the orbit slowly. There is essentially no chance of injecting
the anesthetic into one of the extraocular muscles because this procedure uses
a blunt cannula that cannot be pushed into the muscle, Dr. Guyton
With the sub-Tenons route, the surgeon can open the
conjunctiva with a tiny incision, and after placing the blunt cannula directly
into the retrobulbar space, he or she injects a small amount of anesthetic
accomplishing safe and adequate anesthesia absent Wydase, Dr.
For Your Information:
- Robert J. Cionni, MD, can be reached at 10494 Montgomery
Rd., Cincinnati, OH 45242; (513) 984-5133; fax: (513) 984-4240; e-mail:
- David L. Guyton, MD, can be reached at Wilmer 233, Johns
Hopkins Hosp., 600 N. Wolfe St., Baltimore, MD 21287-9028; (410) 955-8314; fax:
(410) 955-0809; e-mail: firstname.lastname@example.org.
- Michael J. Hawes, MD, can be reached at #345, 850 East
Harvard, Denver, CO 80210; (303) 698-2424; fax: (303) 698-2430; e-mail:
- H. Dunbar Hoskins Jr., MD, can be reached at 655 Beach St.,
San Francisco, CA, 94109; (415) 561-8510; fax: (415) 561-8533; e-mail:
- Samuel Masket, MD, can be reached at 7320 Woodlake Ave. Ste.
380, West Hills, CA 91307; (818) 348-6190; e-mail:
- Douglas Petkus can be reached at Wyeth-Ayerst Laboratories,
555 Lancaster Avenue, St. Davids, PA 19087; (610) 902-7336; fax: (610)
- Kenneth J. Rosenthal, MD, can be reached at Waterview Bldg.
Ste. 102, 310 E. Shore Rd., Great Neck, NY 11023; (516) 466-8989; fax: (516)
466-8962; e-mail: email@example.com.