Eye care practitioners are now able to enjoy unparalleled opportunities to help patients by prescribing them much needed medications for assorted ocular conditions. But with this privilege comes new responsibility in the management of ocular disease and the monitoring of outcomes.
Awareness of brand name vs. generic medications is vital—the FDA estimates that seven out of 10 prescriptions written in the United States is for a generic medication.1 That number is impressive when you take into account the number of TV pharmaceutical advertisements and in-person representative office visits. Can you remember the last time a rep ever called on you to detail data on a generic?
The Hatch/Waxman Act of 1984 allowed the FDA to authorize production of generic drugs if bioequivalence was demonstrated.2 But, U.S. trademark laws prevent generic medications from looking identical to their brand name product counterpart.3 Generic medications have the same dosage, intended use, side effects, risks, administration, safety and strength as the original medicine, but they may differ on the flavors, colors or combination of inactive ingredients.
When a patent expires, manufacturers can apply to the FDA for permission to make and sell generic versions of the original product. The FDA requires the generic medicine to show the same strength, quality, purity, potency and identity as the brand name product. Although generic medications cost consumers a fraction of what brand name drugs may cost, they are quite lucrative for the manufacturer. This is because the generic company can manufacture and market a cheaper medication by bypassing the considerable resources already spent on the initial introduction of the drug to market by the brand name manufacturer. These costs include research and development, clinical trials and legal fees to license and protect the product. The more competition that exists—the less expensive the product.4 For example, the generic timolol maleate is prescribed daily at a cost of $150 vs. the brand name 0.15% brimonidine, which is prescribed three times a day at a cost of $873.5
Differing formulas of generic medication is another issue to consider. For instance, one website lists a minimum of six manufacturers of generic versions for a combination of 2% dorzolamide and 0.5% timolol maleate. This is troublesome because neither the doctor nor the patient knows whether the formulations—including fillers, dyes or other non-active ingredients—are the same.6 Choosing the less-than-ideal formulation can have real effects on the patient treatment outcome. The FDA acknowledges that there may be differences in absorption rates, which can vary between 3.5% and 4.5%.7 Although there is no documented proof, it is presumed that this discrepancy falls within the expected tolerances for brand name medications.
Generic medications are not limited to commercial pharmacy. A scan of pharmacy websites reveals several options including preservative-free alternatives of popular glaucoma medications that can be compounded and produced; medications such as acetazolamide 1%, bimatroprost 0.015%, brimonidine 0.1%, dorzolamide 1% and timolol 0.25% can be found. Other products used for the treatment of infection or dry eye are also available.8 In other words, patients can get preservative- and filler-free generic medications at the pharmacy.
Having mentioned these issues, we are in no way implying that generics are a bad thing. A study published in JAMA reviewed 38 published clinical trials comparing brand name medications against generic substitutes, and the researchers found that there was no difference between brand name medications and their generic counterparts.9 The same is true in a study comparing antiepileptic medications.10
Ocular generic studies have also been performed. Sonty and colleagues studied the tolerability of once daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5% and generic timolol maleate gel forming solution 0.5%. The authors concluded that timolol maleate in sorbate was associated with increased stinging and burning upon instillation.12 The generic was more often associated with post- instillation blur, presumably due to the gel forming characteristics. This was a short-term study with no definitive long term consequences. It is interesting to note that timolol hemihydrates is not the same formulation as maleate and should not be substituted generically. But, alas, many pharmacies do.
There are significant quality considerations to take into account, however, when reviewing international studies. Weir and colleagues analyzed the concentration of ciprofloxacin in generic eye drops and discovered that 20% of sales in India were under-potent.11 Undoubtedly, these types of reports and concerns would garner international attention and dialogue.
One question still remains: Should patients know whether their prescription has changed? If a generic substitution is made, does the patient have the right to be informed of this change? The FDA doesn’t require this disclosure, but as doctors, how can we address such concerns? The answer is greater diligence and pristine communication with our patients. We must instruct our patients to carefully review medicine labels and to keep an eye out for a change in manufacturer. If they notice any changes with their prescription, they should report such issues immediately to their eye care practitioner or doctor who is responsible for the prescription initiation. The doctor has the ability to represcribe specifying “brand necessary,” but this solution does not address the additional cost of the new prescription. Lastly, keep reviewing the FDA website to stay informed about newly approved generics and their implications.
1. Facts and Myths about Generic Drugs. Available at:
www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingGenericDrugs/ucm167991.htm.(Accessed September 2010)
2.The Hatch-Waxman Act and New Legislation to Close Its Loopholes. Available at: www.cptech.org/ip/health/generic/hw.html. (Accessed September 2010).
3. Stoppler M. Generic drugs: are they as good as brand names? Available at: www.medicinenet.com/script/main/art.asp?articlekey=46204. (Accessed September 2010).
4. Rylander NR, Vold SD. Cost analysis of glaucoma medications. Am J Ophthalmol. 2008 Jan;145(1):106-13.
5. Generic Cosopt. Available at: www.glaucoma.emedtv.com/cosopt/generic-cosopt.html.(Accessed September 2010).
6. Davit BM, Nwakama PE, Buehler GJ, et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009 Oct;43(10):1583-97. (Accessed September 2009)
7. Leiter’s Rx Ophthalmic Compounding. Available at: www.leiterrx.com/pharmacy/Price.pdf. (Accessed September 2010).
8. Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008 Dec;300(21):2514-26.
9. Kesselheim AS, Stedman MR, Bubrick EJ, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs. 2010 Mar;70(5):605-21.
10. Weir RE, Zaidi FH, Charteris DG, et al. Variability in the content of Indian generic ciprofloxacin eye drops. Br J Ophthalmol. 2005 Sep;89(9):1094-6.
11. Sonty S, Mundorf TK, Stewart JA, et al. Short-term tolerability of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in glaucoma and/or ocular hypertension: a prospective, randomized, double-masked, active-controlled, three-period crossover pilot study. Clin Ther. 2009 Oct;31(10):2063-71.