FDA: Updated Safety Alert Regarding Benzocaine-Associated Methemoglobinemia

Since 2009, 119 cases of benzocaine-associated methemoglobinemia have been reported
Since 2009, 119 cases of benzocaine-associated methemoglobinemia have been reported

Over-the-counter (OTC) oral products containing benzocaine should not be used to treat children <2 years old as these products carry significant safety risks such as the possibility of methemoglobinemia, according to the Food and Drug Administration (FDA). As such, the Agency is urging manufacturers to stop marketing OTC oral drug products containing benzocaine for teething to this patient population.

In addition, the FDA has asked manufacturers of OTC benzocaine-containing oral drug products to make changes to the labeling with regard to use in adults and children over the age of 2. These changes include:

  • Adding a warning about methemoglobinemia
  • Adding contraindications directing consumers not to use the product for teething and not to use it in children <2 years old
  • Revising the directions to clearly state that the product should not be used in children <2 years old

In previous communications, the FDA had warned the public about reports of methemoglobinemia in individuals  using OTC benzocaine gels and liquids as well as benzocaine sprays for medical procedures. "Because of the lack of efficacy for teething and the serious safety concerns we've seen with over-the-counter benzocaine oral health products, the FDA is taking steps to stop use of these products in young children and raise awareness of the risks associated with other uses of benzocaine oral health products, " said FDA Commissioner Scott Gottlieb MD. "In addition to our letters to companies who make these products, we urge parents, caregivers and retailers who sell them to heed our warnings and not use over-the-counter products containing benzocaine for teething pain."

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The FDA is also requiring manufacturers of all prescription local anesthetics to standardize warning information about the risk of methemoglobinemia in product labeling across this class of products. Healthcare professionals who use local anesthetics are being advised to minimize the risk of methemoglobinemia by monitoring patients for signs and symptoms, using co-oximetry when possible, and having resuscitation equipment and medications available, including methylene blue. Patients at increased risk for methemoglobinemia include those with breathing problems (i.e., asthma, bronchitis, emphysema, smokers), heart disease, patients with certain inborn deficits (i.e., glucose-6-phosphodiesterase deficiency, hemoglobin-M disease, NADH-methemoglobin reductase [diaphorase 1] deficiency, and pyruvate-kinase deficiency), and the elderly. 

If lidocaine is used, healthcare staff should be familiar with appropriate dosing, proper administration techniques, and safety monitoring; benzocaine sprays are not FDA-approved to numb mucous membranes of the mouth and throat or to suppress the gag reflex during medical procedures. A study comparing the relative ability of benzocaine and lidocaine to make methemoglobin showed that benzocaine generated much more methemoglobin than lidocaine in a red blood cell model.

With regard to OTC products, clinicians should instruct patients looking to use benzocaine-containing products to apply only a small amount and not to use the product more than 4 times per day; signs and symptoms of methemoglobinemia may appear within minutes to 1–2 hours after use. Medications, foods, and water containing nitrites and nitrates may also induce methemoglobin formation that may be additive to that formed with benzocaine products. 

Since 2009, 119 cases of benzocaine-associated methemoglobinemia have been reported to the FDA, 4 of which were fatal. The Agency will continue to monitor the safety of benzocaine-containing products and will take further action if necessary. In the meantime, adverse events related to benzocaine and prescription local anesthetics should be reported to the FDA MedWatch program.

For more information visit FDA.gov.