Prompted by Public Citizen Lawsuit, FDA Finally Acts to Protect Infants from Dangerous Benzocaine Teething Gels

Prompted by Public Citizen Lawsuit, FDA Finally Acts to Protect Infants from Dangerous Benzocaine Teething Gels

In 2014, Public Citizen’s Health Research Group petitioned the Food and Drug Administration (FDA) to take regulatory actions that effectively would ban over-the-counter (OTC) infant teething products containing benzocaine and significantly strengthen the warnings in the product labeling of all other OTC benzocaine medications.[1] We sought these actions because benzocaine can cause methemoglobinemia, a rare but potentially fatal blood disorder that impairs the body’s ability to use oxygen.

After more than three years of FDA inaction, Public Citizen sued the agency on Sept. 21, 2017, to compel a response to our petition.[2] In response to the lawsuit, the agency made a commitment to respond by the end of May 2018.

On May 24, the FDA finally responded.[3] The agency agreed with us that OTC oral health care products containing benzocaine should never be used in infants under any circumstances, even with the advice and supervision of a health care professional, because of the risk of methemoglobinemia. The agency also agreed with us that all other OTC benzocaine products should include a warning about the risk of this potentially fatal adverse effect in the product labeling.

What is benzocaine?

Benzocaine is a topical anesthetic (a substance that induces insensitivity to pain) and analgesic. The drug is used to temporarily alleviate pain and discomfort associated with many oral and non-oral conditions. Common oral uses include treatment of sore throat, oral ulcers and teething. Non-oral uses include management of discomfort due to hemorrhoids, burns, poison ivy and earaches.

Benzocaine is sold in a variety of OTC formulations including gels, liquids, creams, lozenges and sprays. These products have been available for several decades, despite the fact that the FDA has never approved these drugs or finalized regulations proposed in 1991 that would permit them to be legally marketed.

A potentially fatal adverse effect

Benzocaine can cause a blood disorder called methemoglobinemia. The disorder prevents red blood cells from carrying oxygen from the lungs to the rest of the body.[4],[5] Exposure to certain drugs, like benzocaine, is the most common cause of methemoglobinemia.[6],[7] Infants appear to be particularly susceptible to developing this drug-induced condition.[8],[9]

Signs and symptoms of the disorder include pale, gray or blue skin; headache; dizziness; rapid heart rate; weakness; and shortness of breath.[10],[11] Symptoms can occur within minutes to hours — even days — after benzocaine exposure.[12],[13] With severe methemoglobinemia, patients may develop seizures, coma and abnormal heart rhythms.[14],[15] It is critical that drug-induced methemoglobinemia be recognized and treated promptly to avoid a fatal outcome.

FDA safety alerts

In a series of safety alerts issued since 2003, the FDA repeatedly has warned about the dangers of benzocaine. Three of these alerts, issued in 2011, 2012 and 2014, addressed OTC benzocaine products for relief of teething pain in infants.[16],[17],[18]

In its 2011 alert, the FDA summarized the 21 reports of methemoglobinemia involving the use of benzocaine gel or liquid OTC products that had been reported to the agency as of March 16, 2011.[19] Of the 21 cases, ten were categorized as life-threatening. Fifteen of the cases involved children, and of these, 11 involved children age two years or younger who were administered benzocaine gel for teething pain. One of the infants died. At that time, the FDA recommended that benzocaine products “not be used on children less than two years of age, except under the advice and supervision of a healthcare professional.”

In an updated 2012 safety alert, entitled “Benzocaine and Babies: Not a Good Mix,” the agency noted that since 2006, it had received 29 reports of benzocaine-gel-related cases of methemoglobinemia.[20] According to the agency, 19 of these cases occurred in children, and 15 of the 19 occurred in children under two years of age.

Although the chance of methemoglobinemia occurring is very low, the serious nature of this condition means that a high potential for harm can result from misuse — or even appropriate use — of benzocaine products given their widespread availability.

Importantly, there is little evidence that benzocaine products are actually effective for treating teething pain. Because the anesthetic effect of benzocaine lasts only minutes, it is unlikely to provide clinically significant relief from teething pain. In the FDA’s 2014 announcement related to topical benzocaine products for treating teething pain, the agency stated that “[t]hese products are not useful for treating sore gums due to teething because they wash out of a baby’s mouth within minutes.”[21] The agency urged parents and caregivers not to use OTC topical medications like benzocaine for teething pain because they can be harmful.

Public Citizen petitions the FDA

In our July 2014 petition to the FDA, we urged the agency to ban the marketing of OTC topical benzocaine products for treatment of teething pain.[22] Citing the FDA’s own data and recommendations from its multiple safety alerts about the risks of benzocaine-induced methemoglobinemia in infants, we emphasized that there is no reason to expose infants and toddlers to dangerous teething medications when the effectiveness of the products has not been established and there are safer, more effective non-drug teething remedies available.

Our petition also urged the FDA to require that the product labeling of all other OTC benzocaine medications advise never to use the products for teething in infants and to warn about the risk of methemoglobinemia.

On Sept. 21, 2017, Public Citizen sued the agency to compel a response to our petition.[23]

FDA’s belated action

Rather than pursuing the specific rulemaking that we had requested in our petition, the FDA instead individually wrote to each manufacturer and distributor of OTC oral health care products containing benzocaine and asked them to cease marketing benzocaine products for teething pain in infants and children younger than two years and to add warnings to the labeling of all other benzocaine products that are similar to those we had sought in our petition.[24] These actions, which the agency announced on May 23,[25] are intended to achieve the same outcomes we sought in our petition. The FDA also stated that if companies do not comply, the agency will initiate action to remove these products from the market.

After the FDA’s announcement, Church & Dwight Co. announced that it was immediately discontinuing the distribution and sale of its widely used Orajel teething products containing benzocaine.[26]

Although we support the FDA’s action, it came too late for some infants and children. According to the FDA, since May 2014 — just before we submitted our petition — at least 35 cases of benzocaine-associated methemoglobinemia had been reported to the agency or in the medical literature, including two deaths.[27] One death occurred in a 4-month-old infant given a benzocaine-containing OTC product for teething. Faster action by the agency may have prevented many of these events. Indeed, the FDA had overwhelming evidence nearly a decade ago that the risks of OTC benzocaine products for teething pain in infants far outweigh their benefits. The agency easily could have completed the regulatory actions requested in our petition years ago.

What You Can Do

Never use any benzocaine product on infants or toddlers, particularly teething gels.

If your child is experiencing teething, use one of the following safer options to alleviate the pain and discomfort, as recommended by the American Academy of Pediatrics:

• Allow the child to chew on teething rings, wet wash cloths, or bananas that have been chilled in the refrigerator (not the freezer).
• Gently rub or massage the child’s gums with your finger.

If you or an older child is using an OTC benzocaine product, be mindful of the risk of methemoglobinemia and immediately stop the product and seek medical attention if any of the following symptoms develop: blue skin, rapid heart rate, headache, shortness of breath, dizziness, lightheadedness or fatigue.

References

[1]Public Citizen. Petition to the Food and Drug Administration regarding over-the-counter benzocaine products. July 28, 2014.https://www.citizen.org/sites/default/files/2209.pdf. Accessed July 6, 2018.

[2]Public Citizen. Public Citizen, Inc. v. Food and Drug Administration (benzocaine). September 21, 2017. https://www.citizen.org/our-work/litigation/cases/public-citizen-inc-v-food-and-drug-administration-benzocaine. Accessed July 6, 2018.

[3]Food and Drug Administration. Final response letter for docket no. FDA-2014-P-1256. May 24, 2018. https://www.citizen.org/sites/default/files/180524_fda_response_letter_to_benzocaine_petition-clean.pdf. Accessed July 6, 2018.

[4]Abu-Laban RB, Zed PJ, Pursell RA, Evans KG. Severe methemoglobinemia from topical anesthetic spray: case report, discussion, and qualitative systematic review. CJEM. 2001;3(1):51-56.

[5]Mansouri A, Lurie AA. Methemoglobinemia. Am J Hematol. 1993;42(1):7-12.

[6]Ashurst J, Wasson M. Methemoglobinemia: a systematic review of the pathophysiology, detection, and treatment. Del Med J. 2011;83(7):203-208.

[7]Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999;34(5):646-656.

[8]Venkateswari R, Ganesh R, Deenadayalan M, et al. Transient methemoglobinemia in an infant. Indian J Pediatr. 2007;74(11):1037-1038.

[9]Lehr J, Masters A, Pollack B. Benzocaine-Induced methemoglobinemia in the pediatric population. J Pediatr Nurs. 2012;27:583-588.

[10]Ashurst J, Wasson M. Methemoglobinemia: a systematic review of the pathophysiology, detection, and treatment. Del Med J. 2011;83(7):203-208.

[11]So T, Farrington E. Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care. 2008;22(6):335-339.

[12]Bong CL, Hilliard J, Seefelder C. Severe methemoglobinemia from topical benzocaine 7.5% (Baby Orajel) use for teething pain in a toddler. Clin Pediatr. 2009; 48(2):209-211.

[13]Food and Drug Administration. FDA drug safety communication: FDA continues to receive reports of a rare, but serious and potentially fatal adverse effect with the use of benzocaine sprays for medical procedures. April 7, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm250040.htm. Accessed July 6, 2018.

[14]Curtis LA, Dolan TS, Seibert EH. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med. 2009;37(1):32-39.

[15]Liebelt EL, Shannon MW. Small doses, big problems: a selected review of highly toxic common medications. Pediatr Emerg Care. 1993;9(5):292-297.

[16]Food and Drug Administration. Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth. April 7, 2011. #http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm. Accessed July 6, 2018.

[17]Food and Drug Administration. Benzocaine and babies: not a good mix. May 31, 2012. http://www.fda.gov/forconsumers/consumerupdates/ucm306062.htm. Accessed July 6, 2018.

[18]Food and Drug Administration. Do teething babies need medicine on their gums? No. June 26, 2014. http://www.fda.gov/forconsumers/consumerupdates/ucm385817.htm. Accessed July 6, 2018.

[19]Food and Drug Administration. FDA drug safety communication: reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth. April 7, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm. Accessed July 6, 2018.

[20]Food and Drug Administration. Benzocaine and babies: not a good mix. May 31, 2012. http://www.fda.gov/forconsumers/consumerupdates/ucm306062.htm. Accessed July 6, 2018.

[21]Food and Drug Administration. Do teething babies need medicine on their gums? No. June 26, 2014. http://www.fda.gov/forconsumers/consumerupdates/ucm385817.htm. Accessed July 9, 2018.

[22]Public Citizen. Petition to the Food and Drug Administration regarding over-the-counter benzocaine products. July 28, 2014. https://www.citizen.org/sites/default/files/2209.pdf. Accessed July 6, 2018.

[23]Public Citizen. Public Citizen, Inc. v. Food and Drug Administration (benzocaine). September 21, 2017. https://www.citizen.org/our-work/litigation/cases/public-citizen-inc-v-food-and-drug-administration-benzocaine. Accessed July 6, 2018.

[24]Food and Drug Administration. Final response letter for docket no. FDA-2014-P-1256. May 24, 2018. https://www.citizen.org/sites/default/files/180524_fda_response_letter_to_benzocaine_petition-clean.pdf. Accessed July 6, 2018.

[25]Food and Drug Administration. FDA takes action against the use of OTC benzocaine teething products due to serious safety risk, lack of benefit. May 23, 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm608325.htm. Accessed July 6, 2018.

[26]Christensen J. FDA warns that benzocaine teething products aren't safe for children. May 23, 2018. https://www.cnn.com/2018/05/23/health/fda-benzocaine-teething-warning/index.html. Accessed July 6, 2018.

[27]Food and Drug Administration. Final response letter for docket no. FDA-2014-P-1256. May 24, 2018. https://www.citizen.org/sites/default/files/180524_fda_response_letter_to_benzocaine_petition-clean.pdf. Accessed July 6, 2018.