Serious Reactions to Oral Pain Relief Products Continue but Labeling Fails to Warn of Risk

April 7, 2011

The U.S. Food and Drug Administration (FDA) continues to receive reports of a serious and potentially fatal side effect associated with use of oral benzocaine pain relief products. The agency is warning consumers and healthcare professionals of the risks, especially to children under two, because product labeling carries no warning.

Use of oral benzocaine products can cause methemoglobinemia, a condition that reduces the amount of oxygen carried through the blood. This is a serious and potentially fatal condition.

Medical professionals use oral benzocaine products as a topical anesthetic to numb the mucous membranes of the mouth and throat during medical procedures. Consumers can also purchase oral benzocaine products over the counter for the relief of oral pain such as canker sores, mouth and gum irritation, and teething in children.

After 247 reports of methemoglobinemia associated with oral benzocaine, the FDA issued a public health advisory on February 10, 2006 warning of the risks. Since then, the FDA has received 72 new reports of serious adverse health events with these products. Of the 319 total cases, there were 7 cases of death and 32 cases categorized as life threatening. Most cases were children less than two years of age treated with benzocaine for relief of pain from teething.

Even though methemoglobinemia is a known side effect of oral benzocaine use and the FDA warned of the risks in 2006, benzocaine products DO NOT carry a warning of methemoglobinemia risks. Consumers and healthcare providers should be aware of these risks and watch for symptoms of methemoglobinemia including pale, gray or blue colored skin, lips and nail beds, headache, lightheadedness, shortness of breath, fatigue and tachycardia.

Oral benzocaine products come in the following forms: Liquid, Gel/Jelly, Solution, Lozenge, Film, Lotion, Ointment, Powder for Suspension, Cream, Tablet, Disintegrating, Swab, Spray, Gum or Paste.

Brand names of some benzocaine products:

FDA Information for Consumers and Caregivers

• Labels of marketed benzocaine products currently do not as of yet contain warnings about the risk of methemoglobinemia, even though the use of benzocaine can cause this serious condition.
• Benzocaine products should not be used on children less than two (2) years of age, except under the advice and supervision of a healthcare professional.
• Store benzocaine products out of reach of children.
• If benzocaine products are used, watch for signs and symptoms of methemoglobinemia, including pale, gray or blue colored skin, lips and nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; and rapid heart rate. If you or your child has any of these symptoms after taking benzocaine, seek medical attention immediately.
• Signs and symptoms of methemoglobinemia may appear within minutes to one or two hours after using benzocaine. Symptoms may occur after using benzocaine for the first time, as well as after several uses.
• The development of methemoglobinemia after treatment with benzocaine gels and liquids has been reported to occur following a single administration of the product.
• Benzocaine gels and liquids should be used sparingly and only when needed, but not more than four (4) times a day. If pain persists despite using the product as labeled, contact your healthcare professional for further evaluation and treatment recommendations.
• Report side effects or medication errors from the use of benzocaine to the FDA MedWatch program.

FDA Information for Healthcare Professionals

• Labels of marketed benzocaine products currently do not as of yet contain warnings about methemoglobinemia, although the use of benzocaine can cause this condition.
• Advise patients and caregivers to use the smallest amount possible to relieve pain and not to apply the product more frequently than four (4) times daily.
• Before recommending benzocaine products, discuss the signs and symptoms of methemoglobinemia with your patients. Advise patients to monitor for signs and symptoms when using benzocaine products, and to seek medical attention immediately if they suspect methemoglobinemia.
• Recognize the signs and symptoms of methemoglobinemia, including pale, gray or blue colored skin, lips and nail beds; headache; lightheadedness; shortness of breath; fatigue; and tachycardia. These indicate a moderate to severe level of methemoglobin and a marked reduction in the oxygen-carrying capacity of the blood. A characteristic color of the blood (chocolate-brown rather than blood red) may indicate methemoglobinemia, but this change is a late sign of the condition.
• Symptoms may appear within minutes to one or two hours after using benzocaine. Symptoms may occur with the first or subsequent applications of benzocaine.
• 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. If blood is drawn to check for methemoglobinemia, an FDA approved co-oximeter should be used to reliably measure methemoglobin.
• Patients who have breathing problems such as asthma, bronchitis, or emphysema, patients with heart disease, and patients who smoke are at greater risk for complications related to methemoglobinemia.
• Infants less than four months of age, elderly patients, and patients with certain inborn defects such as glucose-6-phosphodiesterase deficiency, hemoglobin-M disease, NADH-methemoglobin reductase (diaphorase 1) deficiency, and pyruvate-kinase deficiency may also be at greater risk of developing methemoglobinemia.
• Medications, foods, and water containing nitrites and nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products.
• Report adverse events or medication errors involving benzocaine to the FDA MedWatch program.