ASAM Members Speak on Boxed Warnings to FDA Advisory Committee

by Johanna Zussman-Dobbins | August 11, 2015

On June 8 and 9, the FDA held a Risk Communication Advisory Committee (RCAC) Meeting to discuss the best approaches to communicating information about the fetal effects in product labeling for methadone and buprenorphine. The committee’s aim was to balance the maternal benefits and risks of treatment to best enable patients and providers to make informed decisions about the use of these medications during pregnancy.

ASAM Member Dr. Mishka TerplanASAM member Dr. Mishka Terplan of BHS Baltimore testified on ASAM’s behalf and emphasized the importance of providing evidence-based treatment to pregnant women with opioid addiction. Terplan highlighted the improved health outcomes for both mothers and babies that result from proper treatment of opioid addiction during pregnancy.

In September 2013, the FDA placed a boxed warning, the highest level of warning at their disposal, on the class of extended-release and long-acting opioid analgesics to describe the risk of neonatal opioid withdrawal syndrome (also known as NOWS). Soon after this decision, the FDA received a citizen petition from the National Advocates for Pregnant Women (NAPW) that objected to the boxed warning labeling of opioids used as maintenance treatment for addiction.

Although the FDA issued a response to NAPW’s citizen petition on April 16, 2014, the administration has since given additional thought to the potential impact of labeling changes to methadone and buprenorphine. The FDA decided to seek the help of the RCAC for guidance on how to best communicate the benefit of medication treatment for opioid addiction during pregnancy and the risk of NOWS.

ASAM and ACOG submitted a joint letter to the committee detailing ASAM’s strong opposition to the addition of a black box label to these life-saving medications. In addition, ASAM and ACOG expressed support for the use of methadone and buprenorphine as a standard of care treatment for women who are addicted to opioids before, during, and after pregnancy. Many expert panelists at the RCAC meeting echoed the core points of the ASAM and ACOG letter and expressed concern about the possible effect that would follow the addition of the boxed label to methadone and buprenorphine.

Further presentations on maternal and child health within the context of addiction medicine alarmed the panel about access issues expecting mothers would have to proper treatment. Experts' comments that using medications for opioid use disorder is the standard of care treatment for women who are addicted to opioids, and using these medications before, during, and after pregnancy can lead to better outcomes, including higher birthweight and longer gestational periods for the neonate, were echoed by two ASAM members, Dr. Mishka Terplan of BHS Baltimore and Dr. Marjorie Meyer of the University of Vermont Medical Center.

Ultimately, most panelists expressed that a boxed label would not be appropriate in this case. As Dr. Terplan testified, “the risk of not treating a pregnant woman suffering from opioid addiction far exceeds the expected and manageable risk of treating the woman with methadone or buprenorphine.”

ASAM member Melinda Campopiano, MD, and Addiction Medicine Medical Officer and Branch Chief for Regulatory Programs at SAMHSA pointed out, methadone is more often than not dispensed in clinics where doctors are well aware of the risk of NOWS and adept at communicating it to their pregnant patients. Similarly, she said that buprenorphine is also most commonly prescribed by doctors who specialize in addiction medicine and are capable and experienced in weighing and communicating the risk of NOWS to their patients as well. As with all medicines administered during pregnancy the risks and benefits must be examined and can be weighed by both the doctor and patient appropriately.

Participants emphasized that NOWS is an expected and treatable condition from which no long-term effects for the infant have been described. In contrast, the impact of not treating pregnant women has been clearly characterized including but not limited to lower birthweight and prematurity.

So while many at the meeting see the benefit of informing doctors and patients of the risk of NOWS in order to assist in immediate identification and treatment, they felt a boxed label would be inappropriate and detrimental to the health of mothers and neonates and focused their discussion on alternative routes of communication at the FDA's disposal. This included suggestions to share information about NOWS in the ‘Warnings and Precautions’ or ‘Use in Specific Populations’ sections of the prescription information or to consider careful media campaigns to disseminate information about NOWS to doctors and the public. Stay tuned for updates communicating the risk of NOWS and the FDA’s decision.

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