Report from the AAP and the FDA
By Rae Brown, MD
The Section on Anesthesiology and Pain Medicine of the AAP has been active in the last quarter providing comment and leadership with the SPPM on many areas within Pediatric Pain Medicine.
Since the Fall of 2015, the AAP has been working with the FDA to clarify the role that codeine has played when used as an analgesic in children. Examination of the adverse event database has revealed more than ten cases of death after the use of codeine in children. Many of these deaths were after tonsillectomies and the age distribution of the children involved included patients up to age twelve. These adverse outcomes, specific to codeine, are thought to be related to genetic variability in the drug’s metabolism to morphine. Rapid metabolizers are capable of increasing the serum concentration of morphine dramatically and, especially in infants, can produce apnea and death.
During the last two years, members of the Section have met with the FDA in public forums concerning this opioid. Recently, the Agency responded by issuing a warning about the use of codeine in children less than twelve. This communication has the effect of essentially contraindicating the use of codeine in infants and children. This action is a remarkable effect of child advocacy and will save lives.
The Practice of Pediatric Pain Medicine
During the last year, the need to provide pain management services to larger populations of children has become clear. The number of practitioners trained in Pediatric Pain Medicine has been static; however many children, especially children of color, are not being served. The AAP is interested in expanding the opportunity for training in Pain Medicine in any way that is feasible. One thought has been to offer an avenue for fellowship training in pain medicine to pediatricians. The Section has taken a leadership role in these discussions as have the leaders of the SPPM. The road that this would open would include Board Certification in Pediatric Pain Medicine for future Anesthesiology Fellows and for Pediatricians trained in the comprehensive management of pain. This would be an advance for the field and the SPPM and the SOA would be in close collaboration throughout the multiyear process.
Abuse Deterrent Formulations (ADF) of Opioids
During 2016 – 2017 the FDA Advisory Committee on Analgesics reviewed more than ten New Drug Application for opioids with technology purported to reduce the risk of abuse by the intranasal or the intravenous route. Most of these formulations were viewed to be safe and effective as analgesics, leading to their marketing by the drug sponsor. There are currently no opioids that have been approved to be specifically marketed as abuse deterrent.
The discussions concerning the usefulness and the safety of the ADF formulations are ongoing. During the last half of 2017 and extending into 2018, the Agency has dramatically slowed the rate of evaluation of ADF formulations, despite ten NDAs in the queue. One of the originally marketed products, OxyContin, is labeled for use in children twelve and older despite the considerable scientific information which contraindicates long term opioid use for chronic pain in children or adults. The use of these ADF formulations has posed ongoing problems that were not considered in the initial planning between the FDA and Industry. One concern at this juncture is the continued rise in deaths from opioids. It is possible that ADFs have forced a transition in some from prescription drugs to heroin and illicit fentanyl. Additionally, in the past some clinicians have interpreted abuse deterrent to mean 'addiction proof'. These formulations were not designed to be addiction proof and they are not. They are not safer than formulations without the ADF moniker. The role that the ADF formulation drugs will play in pain medicine going forward is currently unclear.
The AAP works closely with the FDA to assure the safety of drugs and devices to be used in children. The Section on Anesthesiology and Pain Medicine plays a significant role in discussions concerning changes in the current regulatory strategy about the Agency’s actions for children. I would encourage anyone interested in advocating for adequate and safe pain management for children consider joining the AAP.