43 Attorneys General: New Black Box Warning Needed to Prevent Neonatal Death

Posted 14 May 2013 | By Alexander GaffneyRF News Editor

The National Association of Attorneys General, an organization comprised of all state attorneys general, has sent a letter to US Food and Drug Administration (FDA) Commissioner Margaret Hamburg asking her to add a black box warning to all narcotic analgesics in the hopes of reducing risks to newborn children.

The Letter

At issue for the 43 signatories of the letter is the potential for opioid abuse by pregnant women to lead to Neonatal Abstinence Syndrome (NAS), a syndrome that occurs when infants are suddenly cut off from their existing supply of opioids, which were found in the mother's blood and supplied to the fetus through the umbilical cord.

Side effects can be severe and even deadly, and include tremors, vomiting, seizures, weight loss, irritability, hyperactivity, failure to put on weight and other autonomic nervous system disorders.

Worse, the attorneys note that, "There is still sparse scientific data as to optimal treatments for NAS in either the ante or post-partum settings," leaving doctors with few good options with which to treat affected neonates.

The officials continue that regulators should require the use of a "black box warning" for all opioid analgesics in the hopes of making patients aware of the serious risks associated with opioid use and abuse while pregnant.

"Possible content for the warning might be, 'WARNING: Use of Narcotic Analgesics in Pregnant Women May Cause Neonatal Abstinence Syndrome,'" the AGs suggested.

What are Boxed Warnings?

Boxed warnings are frequently required by FDA to ensure that extraordinary risks are conveyed to consumers and are not missed by a patient or physician skimming a label.

For example, in February 2013 FDA announced that prescription codeine products would henceforth be required to contain a boxed warning contraindicating their use in children who have undergone a tonsillectomy procedure. Some children were found to be able to metabolize the drug ultra-rapidly, causing them to overdose and die.

FDA notes three independent scenarios under which it would require a boxed warning:

  • "There is an adverse reaction so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug."
  • "There is a serious adverse reaction that can be prevented or reduced in frequency or severity by appropriate use of the drug."
  • "FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted."

The letter's request would seem to be aimed at meeting the second of the three standards in that it notes the severity of the adverse reactions and notes the potential benefits of educating consumers. It does not call for a program to ensure safe use of the drug, which is typically contained within a Risk Evaluation and Mitigation Strategies (REMS) program.

The letter does not require or request Hamburg to respond by a particular date.


Regulatory Focus newsletters

All the biggest regulatory news and happenings.

Subscribe