When choosing antibiotics and anti-inflammatories for your perioperative care, consider the potential side effects.
John A. Hovanesian
Eye care practitioners should prescribe generic agents cautiously, as
harmful side effects have been known to occur with these biologically
equivalent alternatives, according to some clinicians.
The U.S. Food and Drug Administration approval process for generic
medications requires only proof of bioequivalence; clinical studies on these
medications are conducted neither on animals nor on humans to demonstrate
safety or efficacy. While similar concentrations of active ingredients must be
demonstrated, inactive ingredients may vary widely and have unknown, sometimes
toxic, effects on the eye, Primary Care Optometry News Editorial
Board Member John A. Hovanesian, MD, FACS, told PCON in an interview.
Paul M. Karpecki
Therefore, practitioners who prescribe these medications must provide
informed consent on all of their patients’ pre- and postoperative
medication options, which may be a daunting task considering all of the changes
occurring in ocular surgery, according to PCON Editorial Board member Paul M.
Karpecki, OD, FAAO.
“There are so many changes that have occurred recently in terms of
medications and protocols that there is a lack of confidence in
comanaging,” he said in an interview.
Risks of generics
The cost benefit of using generics is universally known. Unfortunately,
the term “generic equivalency” is an oxymoron, according to Dr.
Hovanesian, and studies have shown that brands are safer and tend to work
For example, among nonsteroidal anti-inflammatory drugs (NSAIDs),
corneal melts and surface toxicity are frequently seen with generic ketorolac
as opposed to branded Bromday (bromfenac, Ista), Acular (ketorolac
tromethamine, Allergan) and Nevanac (nepafenac, Alcon), Dr. Hovanesian said.
Anterior chamber cell and flare post cataract surgery.
Images: Karpecki PM
“But there’s incredible pressure on patients to go generic or
even switch a nongeneric medicine to a generic,” he said.
Patients get pressure from pharmacists who may receive incentives or
compensation for switching patients to generics and may be under pressure to
promote generics from the pharmacy owner, Dr. Hovanesian said. Promoting
generics is also an easy way for pharmacists to achieve a much higher profit
margin. Moreover, there is pressure from patients’ drug plans, as well, he
Dr. Karpecki added, “It’s unfortunate, because people who can
afford only generics are usually the people who can least afford to have
something go wrong, too.”
Synechiae caused by iritis.
Nuclear sclerotic cataract
Corneal toxicity caused by a medication: medicamentosa.
Iritis with posterior synechiae.
“On top of all of this,” Dr. Hovanesian added, “there
seems to be a false perception among patients that eye drops are not real
medicine to begin with, and which product they go with ultimately will not have
that much of an effect. So why not go cheaper?”
There is also incredible pressure on patients to switch to generics
because of the “donut hole” of Medicare Part D — the period of
time for each Medicare beneficiary where prescription coverage is theoretically
absent — as such that patients will want the cheapest possible option
because they will be paying out of pocket, he said.
However, there have been a few changes to Medicare Part D recently that
have altered this dynamic.
First, Medicare beneficiaries, in 2011, became eligible to receive a 50%
discount at the pharmacy on brand name drugs and only a 7% discount on
equivalent generics, Dr. Hovanesian said.
Second, the full Medicare-negotiated price of brand-name products, not
the 50% discounted price, was able to be counted toward the patient’s true
out-of-pocket expenses. This means that the full, nondiscounted price is
counted toward that $2,850 goal that will enable a beneficiary to exit the
Whereas, third, only the actual amount paid for generics (93% of full
price) is applied toward the deductible, he said.
“From a strictly financial point of view, generics are less
expensive, yes, but not necessarily a better value — especially for those
stuck in the donut hole,” Dr. Hovanesian said. “Patients in the donut
hole may find it more beneficial, or of better worth, to pay an extra $40 for
branded medications in order to exit the donut hole quicker.”
Antibiotics are generally used 1 to 3 days before and 1 week after
surgery. After 1 week, the wounds are usually sealed and no longer require
antibiotics, according to Dr. Hovanesian.
“It’s also important to note that the trend toward the use of
later-generation fluoroquinolones, such as moxifloxacin and gatifloxacin, is
reversing,” he said. “Surgeons are now using less expensive, older
fluoroquinolones, such as ofloxacin, and other classes that are more effective
against methicillin-resistant Staphylococcus aureus, such as
polymyxin or trimethoprim, aminoglycosides (gentamicin and tobramycin) and
Dr. Karpecki agreed with Dr. Hovanesian, except on the matter of the
later-generation fluoroquinolone, besifloxacin, “which has seen double
digit growth across the board.”
“There is also,” Dr. Hovanesian added, “a current trend
toward intracameral antibiotics, which may further reduce risk of postoperative
Dr. Karpecki agreed, but felt it was important to note that this trend
is largely European, and not yet widely adopted in the U.S.
Steroids work to reduce the conversion of cell membrane phospholipids to
arachidonic acid, which is a pro-inflammatory mediator, Dr. Hovanesian said.
“In the past, steroids alone were considered to be all that was
necessary to control inflammation,” he said, “but NSAIDs are now
considered essential to reduce risk of cystoid macular edema (CME).”
Dr. Karpecki agreed. “I feel it is best to begin the medications
ahead of time,” he said. “Research supports a decrease in CME with
prophylactic treatment via an NSAID in cataract patients with nonproliferative
“Most surgeons use both steroids and NSAIDs together, but NSAIDs
alone may replace steroids as comfort grows,” Dr. Hovanesian said.
“They work on different mechanisms of actions,” Dr. Karpecki
said. “So I think there’s added benefit. And some of the newer NSAIDs
have almost an anesthetic effect followed by an analgesic effect, which creates
a great patient response.
“However, if you look at any sort of neurosurgery, steroids play a
critical role,” he said. “And even though surgeons are successfully
making smaller and smaller incisions, I still think there’s going to be a
critical role for immunological suppression at the arachidonic acid level.
NSAIDs will continue to be the mainstay. Dosing of steroids may go down, but I
don’t see NSAIDs being used alone for some time.”
According to Dr. Hovanesian, steroids can be dosed from once daily, as
with Durezol (difluprednate, Alcon), the strongest steroid, to four times daily
with more traditional choices such as Pred Forte (prednisolone acetate,
Ester-based steroids, such as Lotemax (loteprednol, Bausch + Lomb), are
also effective and may have less risk of IOP rise without much compromise in
potency, he said.
“Lotemax is now available as an ointment, though ointments are not
used after cataract surgery because of the risk of causing an aggressive, early
inflammatory reaction known as toxic anterior segment syndrome, which sometimes
occurs with hypopyon,” he said.
Dr. Karpecki supports the use of Lotemax ointment. In a trial with 803
patients using Lotemax ointment (Comstock and colleagues), he said there were
no cases of toxic anterior segment syndrome.
“I don’t think the research indicates the syndrome
occurring,” he said. “I realize that ointments weren’t used in
the past, but this one is preservative-free, and that could be one big
Dr. Hovanesian usually applies steroids up to 3 days preoperatively, and
postoperative durations of treatment can vary anywhere from less than 1 week
(if a potent NSAID is used) to about 4 weeks.
As an exception, Dr. Karpecki added, if working with Crystalens (Bausch
+ Lomb), treatment will actually continue out to 2 months.
NSAIDs, according to Dr. Hovanesian, work to inhibit the cyclo-oxygenase
conversion of arachidonic acid to prostaglandins, which, like arachidonic acid,
are pro-inflammatory mediators, and reduce CME. CME occurs when fluid and
protein deposits collect on or under the macula, causing it to thicken and
swell, from a rare event to 1% incidence.
NSAIDs are especially essential in diabetics, patients with epiretinal
membranes, inflamed eyes or anyone with increased vascular permeability due to
prior inflammation or vascular disease, he said.
They should be applied up to 3 days before surgery and 1 week to 3
months postoperatively, depending on the custom and comfort of the surgeon, he
said. – by Daniel R. Morgan
- Comstock TL, Paterno MR, Singh A, Erb T, Davis E. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clinical Ophthalmology. 2011;5:177-186.
For more information:
- John A. Hovanesian, MD, FACS, can be reached at Harvard Eye Associates, 24401 Calle De La Louisa, Suite 300, Laguna Hills, CA 92653; (949) 951-2020; fax: (949) 380-7856; email@example.com.
- Paul M. Karpecki, OD, FAAO, can be reached at Koffler Vision Group, Eagle Creek Medical Plaza, 120 N. Eagle Creek Dr., Suite 431, Lexington, KY 40509; (859) 263-4631; firstname.lastname@example.org.
- Disclosures: Dr. Hovanesian is a consultant to Bausch + Lomb and Ista. Dr. Karpecki is a paid consultant to Bausch + Lomb, Alcon Labs and Ista.