We appreciate the interest from Greenberg and associates in our article “Avastin Doesn’t Blind People, People Blind People,” published in the February 2012 issue of the American Journal of Ophthalmology . We agree that there will always be the risk of contamination when compounding a medication and that generally there is a lower risk of contamination from a drug manufactured by a pharmaceutical company than one compounded in a pharmacy. However, in this situation, the risk of contamination comes from transferring a drug manufactured by a pharmaceutical company into a syringe. Compared with a ranibizumab transfer performed in the nonsterile environment of a clinic, the transfer of bevacizumab should have a much lower risk of contamination because it is performed using a laminar flow hood and an aseptic technique. Our statement in the Perspective, which was referenced in their letter, that the administration of bevacizumab is safer than ranibizumab deals with the advantage of the air quality and technique used in the preparation of bevacizumab compared with the standard preparation of ranibizumab. However, if the compounder fails to follow the recommended guidelines for preparing bevacizumab, then the risk of contamination of multiple patients is higher with bevacizumab. Endophthalmitis will never be eliminated totally from clinical practice, but endophthalmitis resulting from a compounding mistake should never be tolerated.
The goal of our article was to provide a basic overview of United States Pharmacopeia 797 as it relates to the appropriate compounding or repackaging of Avastin (Genentech/Roche, South San Francisco, California, USA) for intravitreal injection and to provide specific recommendations to prevent microbial contamination by the preparer. We had no intention of entering into the debate over which anti–vascular endothelial growth factor drug a physician should prescribe, which is a decision best made between the physician and the patient. We also had no intention of comparing the safety of one drug versus the other, which is being addressed by ongoing comparative studies and was addressed by another recent Perspective in the Journal. As Greenberg and associates acknowledge in their letter, economics will continue to play a role in the drug selection process between repackaged Avastin and agents approved by the Food and Drug Administration, such as Lucentis (Genentech/Roche) or Eylea (Regeneron, Tarrytown, New York, USA). Keep in mind that not all patients who are financially disadvantaged qualify for free drug or copay assistance and that there is widespread use of repackaged Avastin outside of the United States. The rhetorical question we always hear asked is, “Which drug would you use if price wasn’t the issue?” This question has no answer because price is always an issue, whether it’s an issue for the patient or the payer. In the end, we all end up paying. The more appropriate question is, “Which drug would you use if you had to pay out of pocket for the drug?” The answer to this second question is fairly obvious. Most of us would use Avastin, but we would want it prepared safely.
It is also important to note that repackaged Avastin is used not only for wet age-related macular degeneration or macular edema occurring after retinal vein occlusions, which are the Food and Drug Administration-approved indications for Lucentis. Repackaged Avastin also is used for other off-label ophthalmic indications, such as diabetic macular edema, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity. The off-label use of drugs in ophthalmology and general medicine is extremely common, legal, necessary, and expected. The importance of compounding and repackaging has never been greater than in the present pharmaceutical environment, where there are current shortages for so many different manufactured drugs. Adhering to optimal compounding procedures as discussed in our Perspective will ensure that pharmacists and physicians provide the best possible care for patients.