Topical Benzocaine Associated With Methemoglobinemia

Neil Osterweil

Disclosures

April 07, 2011

Topical benzocaine spray

April 7, 2011 (UPDATED April 12, 2011) — Topical benzocaine sprays, gels, and liquids used as anesthesia during medical procedures and for analgesia from tooth and gum pain may cause methemoglobinemia, a rare but serious and potentially fatal condition, the US Food and Drug Administration (FDA) announced on April 7.

Children younger than 2 years appear to be at particular risk, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.

"In the most severe cases, methemoglobinemia can result in death. Patients who develop methemoglobinemia may experience signs and symptoms such as pale, gray or blue colored skin, lips, and nail beds; headache; lightheadedness; shortness of breath; fatigue; and rapid heart rate," the advisory states.

Methemoglobinemia cases have occurred mainly in children aged 2 years and younger who were treated with topical benzocaine gels for relief of teething pain. The signs and symptoms may occur after a single application or multiple applications, and can begin within minutes or hours of application.

The effect does not appear to be dose-related, because many reported cases occurred after administration of a single benzocaine spray.

Benzocaine product labels do not currently contain a warning about the risk for methemoglobinemia, according to the FDA.

FDA Recommendations

  • Do not administer benzocaine products to children younger than 2 years unless under the guidance and supervision of a healthcare professional.

  • Healthcare professionals should carefully monitor patients who receive benzocaine sprays for signs of methemoglobinemia during the procedure, and for at least 2 hours after application.

  • "Methemoglobinemia can cause unreliable oxygen saturation readings on a standard 2-wavelength pulse oximeter when used to assess the amount of oxygen bound to hemoglobin," the FDA notes. "If blood is drawn to check for methemoglobinemia, an FDA-approved co-oximeter should be used to reliably measure methemoglobin."

  • When using benzocaine for oral analgesia, the recommendations in the product label should be followed.

  • Benzocaine products should be stored out of reach of children.

The FDA said it is continuing to monitor the safety of topical benzocaine products.

Data Summary

Through March 16, 2011, a total of 21 cases of methemoglobinemia associated with the use of over-the-counter benzocaine gel or liquid products were reported to the FDA's Adverse Event Reporting System (AERS), including 10 "life-threatening" cases (reported methemoglobin level > 55%) and 6 "serious" cases (reported methemoglobin level 30% - 55% or reported treatment with methylene blue). There was also 1 reported death with unclear contribution of benzocaine gel, and 4 cases in which information was insufficient to determine the severity of the methemoglobinemia.

Most cases of methemoglobinemia involved use of over-the-counter benzocaine products at home; 15 cases involved pediatric patients (including 11 patients aged ≤ 2 years), and 6 involved adults. Of the 14 cases that reported information regarding the amount of benzocaine administered, 5 patients had used the product in accordance with the label recommendations, and 9 appeared to have used the product inappropriately or excessively.

Of the 5 cases reporting use in accordance with label directions, 2 cases (1 life-threatening case in an adult and 1 serious case in a 1-year-old child with normal methemoglobin-reducing capacity) occurred after a single administration of benzocaine gel to the oral mucosa.

Onset of symptoms or diagnosis of methemoglobinemia generally occurred from a few minutes to 1 to 2 hours after application of benzocaine gel, with the first or subsequent applications. Cyanosis was the most-often reported sign, and other signs and symptoms included irritability, lethargy, difficulty walking, numbness of the hands and feet, and syncope.

More information is available at the FDA web site.

Adverse events related to topical benzocaine products should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

Laurie Barclay, MD, contributed to the news brief.

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