Benzocaine is a local anesthetic used in some oral over-the-counter products approved by the Food and Drug Administration (FDA) to treat conditions such as teething pain, canker sores, and mouth pain. It can also be found in certain prescription local anesthetics that are administered by injection as numbing agents or applied directly to the skin or mucous membranes. Health care professionals also sometimes use sprays containing benzocaine for non-FDA approved use, such as for numbing mucous membranes in the mouth and throat during certain procedures.

There have been reports in the literature since 1971 of an association between benzocaine and a rare but potentially fatal adverse effect known as methemoglobinemia. The FDA first issued a warning about this association in 2006. Now the agency is requiring manufacturers to add a warning about methemoglobinemia to the labeling of drugs containing benzocaine and to stop marketing these products for teething pain in infants or for use in children under two years of age. This action was based on an FDA review of 119 case reports, including four deaths, reported to the agency or in the literature between February 2009 and October 2017, as well as on results of an in vitro study conducted by the FDA.

Methemoglobin is a form of hemoglobin in which the iron atoms have become oxidized, leading to a sudden decrease in oxygen available to the tissues. Methemoglobinemia occurs when the production of methemoglobin is unusually high. Although some people experience methemoglobinemia secondary to a genetic variation, the condition is more commonly acquired after exposure to certain drugs (such as benzocaine and other anesthetics, as well as antibiotics such as dapsone and chloroquine) or chemicals (nitrobenzene and nitrites).

The signs and symptoms of moderate-to-severe methemo-globinemia include pale, gray, or bluish skin, lips, and nail beds; headache; lightheadedness; shortness of breath; fatigue; and tachycardia. A change in the color of the blood (to chocolate brown) may occur as a late sign. These signs and symptoms can appear within minutes or up to two hours after administration of the benzocaine product. Methemoglobinemia is not dose related and can occur after the first use of a benzocaine product. Some patients may be at higher risk for developing methemoglobinemia, including those with asthma; bronchitis; emphysema; heart disease; a history of smoking; and inherited defects such as glucose-6-phosphodiesterase deficiency, hemoglobin-M disease, NADH-methemoglobin reductase (diaphorase 1) deficiency, and pyruvate-kinase deficiency). Older adults also seem to be at higher risk for the condition.

Nurses should tell parents to avoid using benzocaine products to treat teething pain in infants and oral pain in children under the age of two. Parents should be instructed to treat teething pain according to American Academy of Pediatrics guidelines (use a firm rubber teether or gently rub a finger along the child's gums, for example).

Oral benzocaine products include Anbesol, Orajel, and Topex, among others. If a benzocaine product is prescribed for adults or children over the age of two, nurses should advise patients and their families to use the drug sparingly. The product should not be used more than four times per day. Patients should also be taught the signs and symptoms of methemoglobinemia and to seek medical help immediately if they occur.

Although the FDA discourages off-label use of benzocaine products, if they are used off label as a spray prior to a procedure (such as transesophageal echocardiogram, endoscopy, or intubation), health care professionals should be aware of the risk of methemoglobinemia and assess the patient for its signs and symptoms. Although benzocaine appears to carry the highest risk of methemoglobinemia, prescription local anesthetics (articaine, bupivacaine, chloroprocaine, lidocaine, mepivacaine, prilocaine, ropvacaine, and tetracaine) have also been associated with this severe adverse effect, and health care providers should consider this possibility. During use of benzocaine and other local anesthetics, the agency encourages the use of an FDA-cleared, multiple wavelength pulse co-oximeter to reliably measure oxygen saturation, because methemoglobinemia can produce unreliable oxygen saturation readings on standard two-wavelength pulse oximeters. Emergency equipment should be on hand.

If methemoglobinemia occurs, nurses and other health care providers should be aware that the antidote is methylene blue, which reduces methemoglobin to oxyhemoglobin. Methylene blue is used if methemoglobin levels are greater than 20% to 25%, or if the patient is symptomatic. The recommended dose as an antidote for drug-induced methemoglobinemia is 1 to 2 mg/kg (0.1 to 0.2 mL/kg of 1% solution) intravenously infused over five minutes. Methylene blue has a rapid onset of action, with maximal effects typically seen within 30 minutes. The dose may be repeated in one hour if cyanosis persists. Judicious use of methylene blue is required, as the drug has dose-related toxicities.

To read the full FDA Drug Safety Communication regarding benzocaine, go to https://www.fda.gov/Drugs/DrugSafety/ucm608265. htm.