Because of the depressed economy, the fluctuation of drug prices and non-coverage issues associated with some insurance providers, optometrists frequently are forced to prescribe a generic ophthalmic medication. Here, we’ll examine the approval process of generic drugs as well as discuss several concerns related to cost vs. efficacy and safety.

Generic Drug Approval
The FDA requires that all generic medications be as safe and effective as brand medications. More specifically, generic drugs are required to have the same active ingredient, concentration, dosage, form and route of administration as their brand-name counterparts.¹ However, the most noteworthy concern is that generic drugs are NOT required to have the same inactive ingredients, drop consistency, pH, bottle size, color or preservatives as brand-name drugs.

For generic systemic drugs, this fundamental concern may not be as overwhelmingly significant. In eye care, though, medications are administered directly on the organ being treated. Could the variance in non-active ingredients make a difference in treatment efficacy? In other words, do different inactive ingredients affect drug penetration, homogeneity and absorption into the anterior chamber, or even potentially create cytotoxicity on the ocular surface? Many eye care providers believe that the answer is a resounding “yes.”

Cost Considerations
It costs an estimated $500 million to $1 billion to bring one drug through development and FDA testing in the U.S.¹ Generic drugs are not required to go through the rigors of an FDA trial to demonstrate safety and efficacy. Elimination of extensive FDA testing removes the majority of associated development costs.

Instead, generic drugs must be shown to demonstrate comparable blood concentrations and therapeutic effects to the brand-name drug.¹ But, in ocular drugs, blood concentration levels really aren’t as relevant as in systemic medications. Furthermore, generic manufacturers are only required to report adverse events that originally had been associated with the branded drug.

So, does the savings ultimately justify the potential for decreased efficacy and safety?

Efficacy and Safety
One study compared molecular particle size in generic prednisolone acetate to that in Pred Forte (Allergan).² The authors found that the size of prednisolone particles in Pred Forte was smaller and more uniform, permitting the active ingredient to remain in suspension longer, which ultimately contributed to increased ocular bioavailability.²

A similar study compared the dose uniformity of generic prednisolone acetate to that of Pred Forte.³ Interestingly, when the bottle was stored upright and shaken, Pred Forte failed to meet its declared concentration in 60% of the tests.³

But, of far greater concern, generic prednisolone––under the same handling conditions––failed to achieve its proper concentration in 94% of the tests.³ This high level of variability means that patients on generic prednisolone may receive either too much or too little of the active ingredient throughout a complete dosing regimen.

In addition to ophthalmic steroids, there appear to be several efficacy issues associated with generic topical NSAIDs. Although corneal melting has been documented in patients using both generic and brand-name NSAIDs, the most severe cases have been associated with generic topical NSAID use.^4-7

In August 1999, a series of severe complications following use of a topical NSAID was reported by members of the American Society of Cataract and Refractive Surgery (ASCRS) in response to a survey.⁸ ASCRS members reported 11 cases of corneal melting associated with topical NSAID use; seven cases were attributed to generic diclofenac and four to Voltaren (Novartis). The duration of treatment varied from six days to 17 months.

This variability of onset suggested that such corneal complications were not due to surface toxicity, but perhaps to other factors including inhibition of keratocyte proliferation, alterations in the expression of key enzymes and reduced corneal sensitivity.^8-10 Corneal subepithelial infiltrates and allergic contact dermatitis are other significant complications that have been more frequently associated with generic topical NSAIDs than their brand-name counterparts.^11-13

We, as primary eye care providers, must weigh the cost benefits of generic medications with their potential safety and efficacy concerns. At times, cost trumps all other considerations––and having one treatment option is better than no treatment at all. Other times, however, the benefits of a branded medication that has gone through strict FDA testing outweigh the cheaper alternatives.

It is up to us to remain aware of the latest research surrounding this topic, as well as our patients’ financial situations, so we can make the optimal treatment selections.

Drs. Karpecki and Shechtman have no direct financial interest in any of the products mentioned.

1. The U.S. Food and Drug Administration. Facts and Myths about Generic Drugs. Available at: www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm167991.htm (accessed December 2, 2011).
2. Roberts CW, Nelson PL. Comparative analysis of prednisolone acetate suspensions. J Ocul Pharmacol Ther. 2007 Apr;23(2):182-7.
3. Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednate ophthalmic emulsion 0.05% versus branded and generic prednisolone acetate ophthalmic suspension 1%. Clin Ophthalmol. 2010 Oct 5;4:1119-24.
4. Wolf EJ, Kleiman LZ, Schrier A. Nepafenac-associated corneal melt. J Cataract Refract Surg. 2007 Nov;33(11):1974-5.
5. Di Pascuale MA, Whitson JT, Mootha VV. Corneal melting after use of nepafenac in a patient with chronic cystoid macular edema after cataract surgery. Eye Contact Lens. 2008 Mar;34(2):129-30.
6. Feiz V, Oberg TJ, Kurz CJ, et al. Nepafenac-associated bilateral corneal melt after photorefractive keratectomy. Cornea. 2009 Sep;28(8):948-50.
7. Montes-Mollon MA, Perez-Rico C, Beckford-Tongren C, et al. Corneal melting and topical NSAIDs. A case report. Arch Soc Esp Oftalmol. 2009 Jun;84(6):311-3.
8. Flach AJ. Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Trans Am Ophthalmol Soc. 2001;99:205-10; discussion 210-2.
9. Mian SI, Gupta A, Pineda R 2nd. Corneal ulceration and perforation with ketorolac tromethamine (Acular) use after PRK. Cornea. 2006 Feb;25(2):232-4.
10. Acosta MC, Berenquer-Ruiz L, Garcia-Galvez A, et al. Changes in mechanical, checmial and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs.  Invest Ophthalmol Vis Sci. 2005 Jan;46(1):282-6.
11. Sher NA, Krueger RR, Teal P et al. Role of topical corticosteroids and nonsteroidal antiinflammaotry druges in the etiology of stromal infiltrates after excimer photorefractive keratectormy. J Refract Corneal Surg. 1994 Sep-Oct;10(5):587-8.
12. Probst LE, Machat JJ. Corneal subepithelial infiltrates following photorefractive keratectomy. J Cataract Refract Surg. 1996 Apr;22(3):281.
13. Mizyazato H, Yamaguchi S, Taira K, et al. Allergic contact dermatitis due to diclofenac sodium in eye drops. J Dermatol. 2011 Mar;38(3):276-9.