Several ophthalmic organizations have collectively sent a letter to the FDA requesting that the agency retain moxifloxacin as Category 1 for outsourcing facility use (503b), citing a demonstrated clinical need for the medication as a bulk substance. The request comes after the FDA, on July 31, gave notice that it intends to remove moxifloxacin and ketorolac from the 503B list of active pharmaceutical ingredients (API) that are allowed to be compounded.
If the FDA is successful in removing moxifloxacin and ketorolac from the 503B list of allowed APIs, ImprimisRx and other 503B outsourcing facilities will no longer be able to produce Current Good Manufacturing Practice (cGMP) manufactured products containing moxifloxacin and ketorolac.
The letter, which was addressed to Janet Woodcock, MD, Director, Center for Drug Evaluation and Research, FDA, was cosigned by leaders of the American Academy of Ophthalmology, the American Society of Cataract and Refractive Surgery, the American Glaucoma Society, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Retina Specialists, the Retina Society, the Macula Society, and the Cornea Society.
Imprimis is urging physicians to sign a petition in an effort to keep moxifloxacin and ketorolac in 503B. That petition can be found here.
In the letter, the ophthalmic organizations citied the Aravind Eye Hospital clinical trial, which compared two doses of moxifloxacin, 250 mcg and 500 mcg, and was shown to be safe in a large case series.[1,2]
This is also the most common concentration used for antibiotic prophylaxis of endophthalmitis following cataract surgery, according to a 2019 ASCRS Survey, with about half of survey respondents replying they used intracameral antibiotics as part of their endophthalmitis prophylaxis regimen.
“Compounded solutions are the source of intracameral moxifloxacin for many American eye surgeons. 503B facilities in the United States supply many Ambulatory Surgery Centers (ASCs) and Hospital Outpatient Departments (HOPDs) with compounded moxifloxacin at 5 mg/ml from bulk substances,” the ophthalmic organizations stated in the letter. “The active pharmaceutical ingredient (API) is only obtained from FDA-registered manufacturers that are inspected by the FDA. This assures, as with FDA-approved finished drug products, certain specifications that must be maintained.”
The organizations added that there is only one manufactured 5mg/ml finished drug product [FDP], topical Vigamox (Novartis), and its authorized generic, Sandoz moxifloxacin 0.5%. Other generics can be confused by the surgeon as moxifloxacin 0.5%, such as Moxeza (Novartis), according to the letter.
“The need for the product is not likely to diminish from deletion from the bulk substance list. Absent availability from FDA-regulated Outsourcing Facilities, repackaged moxifloxacin 5 mg/ml will be made by 503A pharmacies, or by individual surgeon’s preparation of their own intracameral product,” the letter stated. “We understand that there have been complications from misuse of compounded moxifloxacin at too high a dose or prepared from an incorrectly formulated source product. These issues to the best of our knowledge have not been associated with the quality of product from 503B outsourcing facilities, rather from physician dosing errors or use of Moxeza in at least 10 cases.”
“Although we understand the FDA’s desire to promote the use of approved products as the basis for compounded products to protect the health of our patients, we believe that public safety will be reduced by loss of access to bulk moxifloxacin,” the letter continued. “While Vigamox and Moxeza are both FDA-approved products, neither is ideal for intraocular use due to dosage, pH toxicity, inactive components, and particulate concerns.”
1 Haripriya, A., Chang, D., Ravindran, R. Endophthalmitis reduction with intracameral moxifloxacin in eyes with and without surgical complications: Results from 2 million consecutive cataract surgeries. J Cataract Refract Surg 2019, 45:1226-1233.
2 Chang, D., Pranjna, V., Szczotka-Flynn, L., et al. Comparative corneal endothelial cell toxicity of differing intracameral moxifloxacin doses after phacoemulsification. J Cataract Refract Surg 2020; 46:355-359.
3 https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-risks- associated-intraocular-use-compounded-moxifloxacin