Eyeworld CME Supplements

EW JUL 2013 - Supported by Bausch + Lomb

This is a supplement to EyeWorld Magazine that doctors can take a test after reading and receive CME credits for.

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"I personally recommend branded medications to all my patients," said Dr. Mah. An additional issue surrounding generic drugs is the Supreme Court ruling that states that companies that manufacture generic medication are not responsible for the product insert and the label, and are therefore not liable if a patient has a complication with these drugs. This may shift the liability to the prescribing surgeons and their offices, hospitals, and surgical centers. Dr. Mah suggested that it may be necessary to provide written consent or acknowledgement stating that patients prescribed with generic drugs have been informed of and accept the risks of taking medication not backed by efficacy and safety studies. The issues of liability aside, it is a significant comfort to know that there are excellent quality products available, designed to deliver the optimum therapeutic effect with the fewest unwanted side effects, rigorously studied in clinical trials to show efficacy and safety. Figure 7. Strategies to improve ocular drug delivery Lipophilicity can be increased by using unique chemical structures. The chemical nature of bromfenac is hydrophilic, thus formulation pH and vehicle are key to facilitating rapid penetration to produce early and sustained drug levels, which has been accomplished in the new formulation. Meanwhile, nepafenac is a prodrug, a property that allows it to rapidly and safely cross the cornea. Lowering the pH can decrease the charge, increasing lipophilicity, and facilitate corneal penetration of NSAIDs. The newer bromfenac formulation lowers the pH of the original bromfenac formulation, from 8.3 to 7.8 (closer to the 7.4 pH of tear fluid). This decreases the charge, increases the lipophilicity, and so increases the drug delivery into the eye. This strategy has also been used by the new nepafenac formulation showing the importance of this property for topical NSAIDs. A third strategy is to use formulation science to increase viscosity. An example of this is to use a mucoadhesive matrix such as polycarbophil USP, which stays in contact with the conjunctiva and delivers the drug to the surface of the eye over a period of hours, thus increasing the bioavailability of the drug. This is the vehicle used in loteprednol gel. Other medications such as the new nepafenac formulation use guar gum, which acts as a stabilizer, emulsifier, thickening, and suspending agent, or lipid emulsion technology such as the difluprednate formulation to increase viscosity, corneal penetration, and residence time, and so bioavailability. These technologies also mean that the newer drugs do not need shaking—the drug remains suspended evenly. This improves drug delivery so that drop-to-drop variance of drug does not occur. This is especially important considering prednisolone acetate 1%, for example, may vary from 0% drug to 700% depending on shaking or not and bottle inversion. Preservatives – a necessary evil Recent years have seen some controversy over another component of modern drugs— preservatives. However, Dr. Mah called them a "necessary evil," used to prevent microbial activity and prolong the shelf life of drugs. Two primary preservatives are used in antiinflammatory agents: sorbic acid and benzalkonium chloride (BAK). Sorbic acid has long been used in artificial tears because it causes only minimal irritation or damage to the ocular tissues and is thus recommended for sensitive eyes. Meanwhile, according to Dr. Mah, 72% of ophthalmic medications are preserved with BAK. One of the benefits of using this substance with its mild toxicity is that it enhances drug penetration through the cornea by breaking epithelial bonds. This toxicity is dose dependent, and newer anti-inflammatory formulations contain lower concentrations. Not all the same It is important to note that not all medication vehicles are the same. The distinction is particularly important when considering generic drugs. Unlike branded drugs, generics can be approved without clinical studies to show efficacy or safety; rather, they only need to show 80% bioequivalence in the bottle. References 1. McColgin AZ, Raizman MB. Invest Ophthalmol Vis Sci. 1999;40(S289). 2. Mishima H, Masuda K, et al. Prog Clin Res. 1989;31:251-264. 3. Raizman MB et al. Curr Med Res Opin. 2007;23:2325-31. 4. Heier JS, Topping TM, Baumann W, et al. Ophthalmology 2000;107:2034-8. 5. Warren KA, Fox JE. Retina 2008;28:1427-1434. 6. Hariprasad SM et al. Clin Ophthalmol 2009;3:147-154. 7. Chang DF, Tan JJ, Tripodis Y. Risk factors for steroid response among cataract patients. J Cataract Refract Surg. 2011 Apr;37(4):675-81. 8. Bartlett JD, Horwitz B, Laibovits R, Howes JF. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993;9:157-165. 9. Holland EJ, Djalilian AR, Sanderson JP. Attenuation of ocular hypertension with the use of topical loteprednol etabonate 0.5% in steroid responders after corneal transplantation. Cornea 2009;28:1139-1143. 10. Ghate D and Edelhauser HF. Expert Opin Drug Deliv. 2006;3:275-287. 11. Gaudana R. et al. AAPS J. 2010;12:340-360. 12. Coffey MJ et al. Manuscript in preparation. Contact information Chang: dceye@earthlink.net Devgan: devgan@gmail.com Kim: terry.kim@duke.edu Mah: Mah.Francis@Scrippshealth.org Warren: kwarren@warrenretina.com

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