Article Date: 11/1/2009

A Topical Subject
drugs

A Topical Subject

Four topical ophthalmic drugs received FDA approval through the past five months. Here's what you need to know about them.

PAUL M. KARPECKI, O.D., F.A.A.O., LEXINGTON, KY.

From May through to September, the Food and Drug Administration (FDA) approved no less than four topical ophthalmic drugs — that's almost one drug per month — arming us with exciting new options in the treatment of various conditions.

To enable you to retain and attract patients by providing them with the most up-to-date care, this article provides you with an overview of these medications. (See "Patient 'Tips,'" below.)

Besifloxacin ophthalmic suspension 0.6% (Besivance, Bausch & Lomb). Besivance received FDA approval for the treatment of bacterial conjunctivitis in patients age one and older on May 29.1 This chlorinated fluoroquinolone, which has no systemic counterpart,* provides broad-spectrum antibacterial activity against CDC coryneform group G, Corynebacterium pseudodiphtheriticum, Corynebacterium striatum, Haemophilus influenzae, Moraxella lacunata, Staphylococcus aureus, S. epidermidis, S. hominis, S. lugdunensis, S. mitis group, S. oralis, S. pneumoniae and S. salivarius.

In addition, Besivance has demonstrated success in the elimination of methicillin-resistant S. aureaus (MRSA) and methicillin-resistant S. epidermidis in microbiological studies.2 This is significant, as methicillin-resistant bacteria-caused eye disease is on the rise.

For instance, one cross-sectional study revealed that the proportion of MRSA grew from 4.1% in 1998 to 1999 to 16.7% in 2005 to 2006. Further, A total of 78% of these MRSA patients had blepharoconjunctivitis.3

Besivance includes the polycarbophil, edetate disodium, sodium chloride (DuraSite, In-Site Vision Incorporated) vehicle, which increases the amount of time a medication remains on the eye, thus precluding frequent dosing.

In terms of dosing, patients or caregivers are to instill one drop from the 7.5mL size bottle in the affected eye(s) t.i.d., four to 12 hours apart for seven days.1

The most frequently reported adverse event with this bacterial conjunctivitis drug was conjunctival redness, which approximately 2% of patients reported. Meanwhile, 1% to 2% of tients said they experienced blurred vision, eye pain, eye irritation, eye pruritis and headache. (Visit www.besivance.com for further information.)

Ketorolac tromethamine 0.45% preservative free solution (Acuvail, Allergan). The FDA approved Acuvail for the treatment of pain and inflammation post-cataract surgery on July 23.4 (The safety and effectiveness in pediatric patients has not been established.) The non-steroidal anti-inflammatory drug (NSAID) is a new formulation of the company's ketorolac tromethamine 0.5% (Acular), which received an additional indication from the FDA for treating inflammation post-cataract surgery in 1997.

Acuvail, unlike its predecessor, is benzalkonium chloride (BAK)- and edetate-free. The removal of these agents will likely decrease the incidence of drop burning and stinging, making instillation more comfortable than before. In addition, the drug contains carboxymethylcellulose, a viscous molecule, which enables it to not only stick to the ocular surface, but also boost patient comfort upon instillation.4 Further, Acuvail offers a 6.8 pH, which results in enhanced drug availability for absorption.

Patients or caregivers are to instill the drug, which comes in a single-use vial, b.i.d. starting one-day before cataract surgery. The cataract surgery patient is to then continue using it on the day of the procedure and through the first two weeks after undergoing the surgery. (Single-use vials are packaged in six foil pouches, five vials per pouch.)4,5

Because Acuvail is an NSAID, you should be aware of the warnings and precautions, such as slowed or delayed healing time, associated with prescribing this drug class prior to prescribing it to your patients. For a full list of these warnings and precautions, visit www.allergan.com/assets/pdf/acuvail_ pi.pdf.

Bepotastine besilate ophthalmic solution 1.5% (Bepreve, Ista Pharmaceuticals, Inc.). Bepreve received FDA approval for the treatment of allergic conjunctivitis-caused ocular itching in patients age two and older on September 8.6

As a brief aside, the systemic form of the drug has treated urticaria since July 2000 and pruritis since January 2002 in Japan under the name Talion. In 2006, Ista Pharmaceuticals bought the licensing rights to the eye drop formulation for the treatment of allergic conjunctivitis.

Bepreve is a non-sedating, antagonist of the histamine (H1) receptor that stabilizes mast cells and inhibits eosinophil migration into inflamed tissues.6

Patients or caregivers are to instill one drop of the drug, which comes in a 10mL eye dropper, into the affected eye(s) b.i.d.

An interesting finding: Bepreve trials that assessed the Total Non-Ocular Symptoms Score showed effects in some areas, such as excessive tearing, though the drug is not indicated for these conditions.

The most common adverse effect of Bepreve was a transient, mild taste of the drug post-instillation, as reported by 25% of patients.6 Meanwhile, a total of 2% to 5% of patients said they experienced eye irritation, headache and nasopharyngitis (swelling of the nasal passages and the upper pharynx.) (Visit www.istavision.com for further information.)

Patient "Tips"
Regardless of which of these new offerings you choose to prescribe, remember to educate patients on the importance of preventing tip contamination by bacteria that could introduce infections into the eye and lead to vision loss. Specifically, instruct patients to:

  1. Always wash their hands prior to use.
  2. Always replace the tip cover.
  3. Prevent the tip cover from touching any surface.
  4. Never apply while wearing contact lenses.

Ganciclovir ophthalmic gel 0.15% (Zirgan, Sirion Therapeutics). The FDA approved Zirgan for the treatment of acute herpetic keratitis (dendritic ulcers) in patients age two and older on Sept. 16.7

Incidentally, the drug has become the standard of care for the treatment of HSV keratitis for more than a decade in Europe, where it's called Virgan, the company says.

The anti-infective medication, which comes in a 5g tube, works by selectively targeting the replication of herpes simplex virus DNA within corneal cells.

The recommended dosing is two-fold: one drop in the affected eye five times per day until the dendritic ulcer resolves and then one drop in the same eye t.i.d. per day for seven days.

In terms of adverse effects associated with Zirgan, 60% of patients reported blurred vision, 20% reported eye irritation, 5% reported keratitis, and 5% said they experienced conjunctival hyperemia. (Visit www.siriontherapeutics.com for further information.)

Because knowledge of the most current ophthalmic and optometric developments is crucial to the health of your patients and, as a result, your practice, you must stay at the forefront of the latest pharmaceutical and diagnostic advancements.

For instance, now that you know about the latest additions to the topical ophthalmic medication market, you can ensure those patients who present with the aforementioned conditions remain loyal to you. This will lead to referrals and the enhancement of the financial health of your practice. OM

* Researchers believe that much of the bacterial resistance, including resistance to older fluoroquinolones, is attributable to the use of the oral medications in hospital settings and in agriculture. Since Besivacne has no systemic counterpart, this will not be possible.

  1. Bausch & Lomb Receives FDA Approval of Besivance, New Topical Ophthalmic Antibacterial for the Treatment of Bacterial Conjunctivitis ("Pink Eye") www.bausch.com/en/US/corporate/corpcomm/news/besivance_approval.aspx. Accessed Oct. 9, 2009.
  2. Zhang JZ, Cavet ME, Ward KW. Anti-inflammatory effects of besifloxacin, a novel fluoroquinolone, in primary human corneal epithelial cells. Curr Eye Res. 2008 Nov;33(11):923-32.
  3. Freidlin J, Acharya N, Lietman TM, et al. Spectrum of eye disease caused by methicillin-resistant Staphylococcus aureus. Am J Ophthalmol. 2007 Aug; 144(2):313-15.
  4. Allergan Receives FDA Approval for AVUVAIL Ophthalmic Solution for the Treatment of Pain and Inflammation Following Cataract Surgery. http://agn.client.sharegolder.com/releasedetail.cfm? ReleaseID=398556. Accessed Oct. 9, 2009.
  5. Allergan. Highlights of Prescribing Information. www.allergan.com/assets/pdf/acuvail_pi.pdf. Accessed Oct. 9, 2009.
  6. ISTA Pharmaceuticals' Bepreve Receives FDA Approval for the Treatment of Ocular Itching Due to Allergies. http://phx.corporate-ir.net/ phoenix. zhtml?c=121179&p=irol-newsARticle&ID=1329189&highlight=. Accessed Oct. 9, 2009.
  7. Sirion Therapeutics Announces FDA Approval of Zirgan (Ganciclovir Ophthalmic Gel). http://news.prnewswire.com/ViewContent.aspx?ACCT=109&STORY=/www/story/09-16-2009/0005095067&EDATE=. Accessed Oct. 9, 2009.
Dr. Karpecki works in the Corneal/ External Disease and in ocular surface disease research at the Koffler Vision Group in Lexington, Ky. E-mail him at paul@karpecki.com


Optometric Management, Issue: November 2009