Public Citizen Seeks Ban on Benzocaine Teething Gels Associated With Life-Threatening Condition

Health Letter, September 2014

By Michael Carome, M.D., and Roma Rajput

Imagine you’re a parent or caretaker of a 6-month-old baby girl who has begun teething and is now very fussy. You visit your local pharmacy, and in the baby product aisle, you find several over-the-counter (OTC) topical gels containing the drug benzocaine and carrying labels that indicate they are specifically for the treatment of teething pain in infants. You may assume that the availability of such products over the counter — under brand names such as Baby Orajel, Anbesol Baby and Zilactin Baby — must mean they are perfectly safe and effective if used as directed. But your assumption would be wrong, and the consequences of using these products on an infant could be deadly.

On July 28, Public Citizen petitioned the Food and Drug Administration (FDA) to ban the marketing of OTC benzocaine products for treating teething in infants and toddlers because they can cause a rare but potentially fatal adverse reaction — known as methemoglobinemia — and provide little benefit. We also asked the agency to require a warning about this adverse reaction on all OTC benzocaine products intended for use in treating other conditions in older children and adults.

What is benzocaine?

Benzocaine is a topical anesthetic and analgesic used to temporarily alleviate pain and discomfort associated with many oral and non-oral conditions. It is sold in a variety of OTC formulations, including gels, liquids, creams, ointments, lozenges and sprays.

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, insect bites and earaches. Benzocaine spray products, such as HurriCaine and Cetacaine, are used routinely by health care providers to numb the throat of patients prior to medical and surgical procedures involving insertion of tubes or fiber-optic scopes into the esophagus, stomach and trachea.[1]

OTC benzocaine 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 for multiple uses, including “the temporary relief of sore gums due to teething in infants and children 4 months of age and older.”[2] Nevertheless, the agency has allowed companies to continue marketing these products as long as they comply with certain conditions, such as those regarding dosing and labeling, stipulated in the proposed 1991 regulations.

A potentially fatal side effect

Methemoglobinemia is a blood disorder that prevents red blood cells from carrying oxygen from the lungs to the rest of the body.[3],[4] Exposure to certain drugs, such as benzocaine, is the most common cause of methemoglobinemia.[5],[6] Infants appear to be particularly susceptible to developing this condition through drug exposure.[7],[8],[9]

Signs and symptoms of the disorder include pale, gray or blue skin (cyanosis); headache; dizziness; rapid heart rate; weakness; and shortness of breath.[10],[11] Symptoms can occur within minutes or hours of benzocaine exposure — or even days afterward.[12],[13]With severe methemoglobinemia, patients may develop seizures and abnormal heart rhythms or may fall into a coma.[14],[15] Blood tests are needed to confirm the diagnosis.

It is critical that drug-induced methemoglobinemia be recognized and treated promptly, as it can be fatal if left untreated. The most important initial step is to immediately discontinue use of any drug suspected of causing the condition. Moderate to severe methemoglobinemia is usually treated with the intravenous drug methylene blue.[16]

FDA safety alerts

In a series of safety announcements issued from 2003 to 2014, the FDA repeatedly has warned health care providers and consumers about the life-threatening dangers of benzocaine. Two of these announcements, issued in April 2011 and May 2012, specifically focused on OTC benzocaine products for relief of teething pain in infants.[17],[18],[19]

In its April 2011 alert, the FDA summarized the 21 reports of methemoglobinemia involving the use of OTC benzocaine gel or liquid products that had been reported to the agency through its Adverse Event Reporting System (AERS) database as of March 16, 2011.[20] Of the 21 cases, 10 were categorized as life-threatening. Fifteen of the cases involved children, and of these, 11 involved children age 2 or younger who were administered benzocaine gel for teething pain. One of the infants died. The FDA noted that in some cases, the drug had been administered in accordance with the product label, whereas in others the dosing had been inappropriate or excessive. In its announcement, 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.”

The FDA issued an updated safety alert to consumers in May 2012. In that announcement, titled “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.[21] According to the agency, 19 of these most recently reported cases occurred in children, and 15 of the 19 occurred in children under 2 years of age.

In addition to the cases submitted to the FDA’s AERS database, reports of four cases of methemoglobinemia associated with benzocaine teething gels have been reported in the medical literature.[22],[23],[24,[25] The four infants involved in these cases ranged from 6 months to 15 months of age and were administered anywhere from a “pea-sized amount” to excessive amounts of the gel.

In one particularly notable case published in Clinical Pediatrics in 2009,[26] a 15-month-old infant was given a pea-sized amount of Baby Orajel for teething pain by her mother while the baby was hospitalized in an intensive care unit following a medical procedure. Shortly after administration of the benzocaine product, the infant experienced a drop in her blood oxygen level, which the medical staff attributed to a partial lung collapse. The infant’s condition improved after several hours with oxygen treatment.

The following day, after the patient had been transferred out of the intensive care unit, the mother administered another dose of benzocaine gel to the baby’s gums. The infant immediately turned blue and developed a rapid heart rate. She was diagnosed with methemoglobinemia after a blood test and was treated with methylene blue, after which she recovered rapidly.

Additional cases of methemoglobinemia linked to benzocaine use in infants no doubt have gone unreported to the FDA. Furthermore, because this dangerous reaction can occur hours after an infant is given a single recommended dose — and many parents likely use the product before bedtime — the condition may develop while the baby is sleeping and unmonitored by the parents. It is therefore conceivable that fatal cases of methemoglobinemia due to benzocaine use in infants have been mistakenly attributed to other causes such as suffocation and sudden infant death syndrome.

Little benefit not worth the risk

While the chances of methemoglobinemia occurring with benzocaine use are very low, the serious nature of the condition means that potentially great harm can result. Even a product effective at relieving gum pain during teething would not provide sufficient benefit to outweigh the risk of this dangerous reaction. However, there is little evidence that benzocaine products are actually effective for teething. Clinical studies specifically designed to assess benzocaine’s effectiveness in relieving teething pain are lacking.

The anesthetic effect of benzocaine begins within 30 seconds of application and lasts only 10-15 minutes.[27] Because of this short duration of action, benzocaine is unlikely to be effective at providing clinically significant relief from teething pain. The topical anesthetic also may not penetrate deeply enough into the gums to assist in relieving pain.

Well-meaning parents, intent on relieving their baby’s pain, may be inclined to administer benzocaine in amounts or at frequencies that exceed the recommended dose, thereby increasing the infant’s risk of developing methemoglobinemia.

Notably, on June 26, 2014, the FDA issued another safety announcement related to topical products for treating teething, including benzocaine-containing gels. The agency stated that “[t]opical pain relievers and medications that are rubbed on the gums are not necessary or even useful because they wash out of the baby’s mouth within minutes.”[28] The agency urged parents and caregivers not to use OTC topical medications such as benzocaine for teething pain because they can be harmful. The FDA encouraged parents to instead follow the American Academy of Pediatrics’ (AAP’s) recommendations for lessening teething pain:

  • Use a teething ring chilled in the refrigerator (not frozen).
  • Gently rub or massage the child’s gums with your finger to relieve the symptoms.

Public Citizen’s petition to the FDA

In its July 28 petition to the FDA, Public Citizen requested that the agency take prompt action to prohibit the marketing of OTC topical benzocaine products for treatment of teething pain. Citing the FDA’s own data and recommendations from its multiple safety announcements about the risks of benzocaine-induced methemoglobinemia in infants, the petition 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 nondrug teething remedies available.

We argued that merely including warning labels describing the risk of methemoglobinemia on benzocaine teething products would not be sufficient to protect infants from this potentially fatal adverse reaction. Not only is the product typically used at home, where medical care is not readily available, but parents may not be present to monitor for symptoms that may occur hours after use, potentially at night when the family is sleeping.

We also maintained that it would be insufficient to amend the labeling of benzocaine teething products to include instructions not to use them in children under 2, as some manufacturers already have done. Marketing a product over the counter for use in teething while advising against use in children under 2 creates confusion for many unsuspecting parents who still may assume the products can be used in infants at age 6 months, the time teething typically begins. Upon reading a recommendation on the product label to “consult a physician for children younger than 2,” few parents will infer that this apparently benign OTC product, marketed for a condition that affects only babies, harbors potentially fatal risks for their infant.

Public Citizen’s petition also urged the FDA to take two additional actions. First, we asked the agency to require that the labels for all benzocaine products available in liquid or gel forms include the following warning:

Do not use to treat sore gums due to infant teething. Cases of methemoglobinemia have developed among teething infants exposed to benzocaine.

Such a specific warning is needed because parents and caregivers otherwise are likely to use adult OTC benzocaine products to treat infant teething.

Second, we requested that the FDA require warning labels on all OTC benzocaine products stating the risk of methemoglobinemia and listing the signs and symptoms of the life-threatening disorder. Given that the FDA has received more than 300 reports of benzocaine-induced methemoglobinemia associated with non-teething products — some of which have resulted in fatalities[29] — a mandatory warning label is necessary so that consumers and health care professionals are made aware of the signs and symptoms of this condition and know to seek or initiate prompt evaluation and treatment if they occur.

What You Can Do

Never use any benzocaine products on infants. As with all medications, keep benzocaine products out of the reach of young children.

If your infant is experiencing teething, use one of the following safer options to alleviate the pain and discomfort, as recommended by the AAP and urged by the FDA:

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

If these remedies are ineffective for your infant, consult your pediatrician before using any OTC medication, such as acetaminophen.

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


References

[1] Institute for Safe Medication Practices. Benzocaine-containing topical sprays and methemoglobinemia. October 3, 2002. https://www.ismp.org/newsletters/acutecare/articles/20021003.asp. Accessed July 16, 2014.

[2] 47 Fed. Reg. at 22740.

[3] 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.

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

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

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

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

[8] Ibid.

[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 16, 2014.

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

[17] 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 16, 2014.

[18] Food and Drug Administration. Benzocaine and babies: not a good mix. May 31, 2012. http://www.fda.gov/forconsumers/consumerupdates/ucm306062.htm. Accessed July 16, 2014.

[19] 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 16, 2014.

[20] 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 16, 2014.

[21] Food and Drug Administration. Benzocaine and babies: not a good mix. May 31, 2012. http://www.fda.gov/forconsumers/consumerupdates/ucm306062.htm. Accessed July 16, 2014.

[22] 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.

[23] Gentile DA. Severe methemoglobinemia induced by a topical teething preparation. Pediatr Emerg Care. 1987;3:176-178.

[24] McGuigan MA. Benzocaine-induced methemoglobinemia. Can Med Assoc J. October 15, 1981;125:816.

[25] Townes PL, Geertsma MA, White MR. Benzocaine-induced methemoglobinemia. Am J Dis Child. 1977;131(6):697-698.

[26] 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.

[27] VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel and the National Center for Patient Safety. A guidance on the use of topical anesthetics for naso/oropharyngeal and laryngotracheal procedures. http://www.pbm.va.gov/PBM/clinicalguidance/criteriaforuse/benzocaine.pdf. Accessed July 16, 2014.

[28] Food and Drug Administration. Lidocaine viscous: Drug safety communication – boxed warning required – should not be used to treat teething pain. June 26, 2014. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm402790.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed July 16, 2014.

[29] Food and Drug Administration. FDA drug safety communication: FDA continues to receive reports of a rare, but serious and potentially adverse effect with the use of benzocaine sprays for medical procedures. April 7, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm250040.htm. Accessed July 13, 2014.