Compounded pharmaceuticals have been used for decades, but does that mean they are reliable and safe? “Absolutely,” asserted Dante Pieramici, MD. “The literature disagrees,” said Julia Haller, MD.
Compounded pharmaceuticals have been used for decades, but does that mean they are reliable and safe?
“Absolutely,” asserted Dante Pieramici, MD.
“The literature disagrees,” said Julia Haller, MD.
The two argued the pros and cons of using compounded pharmaceuticals-and specifically bevacizumab (Avastin, Genentech) for retinal diseases. With compounding pharmacies accounting for “about 3% of the pharmaceutical market,” they serve a purpose, said Dr. Pieramici, in private practice in Santa Barbara, CA. Fortified antibiotics and intravitreal antibiotics served as precursors to the intravitreal use of compounded bevacizumab (Avastin), he added.
“Essentially, this is just taking a sterile drug from one container to another,” Dr. Pieramici said.
It’s not that simple, countered Dr. Haller, ophthalmologist-in-chief, Wills Eye Hospital; professor and chairperson of the Department of Ophthalmology, Thomas Jefferson University, Philadelphia.
“A literature review reveals a litany of errors, including contamination and infection, with the worse being a multistate outbreak of fungal meningitis,” Dr. Haller said. “Errors in dosage have occurred. In our own field, we know that in Avastin injections, dosages can vary significantly when prepared by compounding pharmacies.”
The incidence of recalls for compounded pharmaceuticals has been on par with that of commercial drug recalls (about 30 a year), Dr. Pieramici said. He added that compounding facilities used to have only state oversight.
“There have been some issues with compounded drugs being used to treat retinal diseases,” he acknowledged, “including sporadic cluster cases of bacterial and fungal endophthalmitis.”
As a result of those incidents, the FDA pushed the congressional approval of the Drug Quality and Security Act (DQSA) to ensure uniformity in compounded pharmaceuticals.
“If you think that has settled everything, it absolutely has not,” Dr. Haller countered. “The DQSA is still a work in progress, particularly since the proposed restrictions create issues with maintaining a supply of compounded and repackaged drugs in our offices. The draft guidance continues to be under discussion by professional groups, including our own American Academy of Ophthalmology.”
Access to compounded drugs can be problematic for patients as well, and the “Fix DQSA” initiative is active, Dr. Haller added.
“We are a long way from achieving the balance that we need for safe and reliably available compounded drugs,” Dr. Haller pointed out. However, she acknowledged compounded drugs are becoming reliable.
“It is incumbent upon us to be scrupulously conscientious,” she said, and remain vigilant about reporting adverse events to the FDA.
A recent study evaluated more than 503,000 intravitreal injections and “found no difference in the rates of endophthalmitis between aflibercept, ranibizumab, and compounded Avastin,” Dr. Pieramici said. “Overall, there were 183 cases of endophthalmitis, which translates to a rate of 0.035%.”
The “safe and efficacious” use of repackaged bevacizumab has been seen in multiple clinical trials, including CATT, IVAN, GEFAL, MANTA, and the DRCR Network’s Protocol T. Dr. Pieramici believes retina specialists “are pretty comfortable with compounded Avastin.”
He cited the 2016 American Society of Retina Specialists’ Preferences and Trends (PAT) survey showing compounded bevacizumab remains the most commonly used, first-line drug in numerous eye diseases”
When the FDA did implement rules regarding compounding pharmacies, it also began overseeing 503B facilities-the type used for compounding bevacizumab, Dr. Pieramici said.
Those facilities “have to follow the same good manufacturing practices as a pharmaceutical manufacturer. They’re inspected by the FDA, report to the FDA, and they follow state laws, and U.S. Pharmacopeia 797,” he said.
Julia Haller, MD
Dante Pieramici, MD
This article was adapted from a debate that Drs. Haller and Pieramici presented at the Retina Subspecialty Day prior to the 2016 American Academy of Ophthalmology Meeting. Drs. Haller and Pieramici reported no financial disclosures related to the topic of this article.