The FDA is again highlighting here safety information previously addressed by the Agency (see http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/printer.cfm?id=40 ), and will make further announcements or take action as warranted by the ongoing review.   At present, the FDA suggests considering the following points about the use of benzocaine sprays in procedures requiring that a tube be inserted in the larynx or pharynx (down the throat, windpipe, or gullet) or in minor surgical procedures performed in these locations.

Considerations

• Benzocaine sprays used in the mouth and throat can result in potentially dangerous levels of methemoglobinemia.
• 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 and may be candidates for other forms of therapy.
• Patients who may have greater tendency for elevated levels of methemoglobinemia, such as all children less than 4 months of age and older patients with certain in-born defects (such as glucose-6-phosphodiesterase (G-6-PD) deficiency, hemoglobin-M disease, NADH-methemoglobin reductase (diaphorase 1) deficiency, and pyruvate-kinase deficiency) may benefit from products with different active ingredients such as lidocaine.
• Patients who receive benzocaine sprays should be given the minimum amount needed, to reduce the risks associated with methemoglobinemia.
• Patients who receive benzocaine sprays should be carefully observed for signs of methemoglobinemia including pale, gray or blue colored skin, headache, lightheadedness, shortness of breath, anxiety, fatigue and tachycardia (rapid heart rate).
• Methemoglobinemia makes a standard device used to assess the amount of oxygen bound to hemoglobin (2-wavelength pulse oximetry) unreliable.  If blood is drawn to check for the condition, a co-oximeter is needed to reliably detect methemoglobinemia. 
• A characteristic color of the blood (chocolate-brown rather than blood-red) can be a danger sign, but these changes are a late sign of the condition.
• Patients suspected of having high levels of methemoglobinemia should be promptly treated.

Methemoglobinemia is a condition where too much of the hemoglobin in red blood cells becomes unable to bind and carry oxygen.  While there is treatment available, until the condition is reversed, oxygen is not effectively delivered throughout the patient’s body.  Patients with methemoglobinemia can suffer effects ranging from headache to cyanosis (turning blue due to lack of oxygen) that can be life-threatening in the most severe cases.  Patients with underlying breathing problems, such as asthma or emphysema, patients with heart disease, and those who smoke may be more susceptible to the problems from methemoglobinemia and may suffer from bad effects from this condition at lower levels of methemoglobin than healthy individuals.  Similarly, some patients may lack or have reduced level of enzymes that help reverse the methemoglobinemia, and they are also more susceptible to risks associated with benzocaine sprays.

The VA health system has announced its decision to remove benzocaine sprays from their practice because they believe other topical anesthetics are less likely to cause methemoglobinemia and because the procedures themselves might cause similar signs, suggesting that methemoglobinemia may occur but go unrecognized in some cases. The FDA has received adverse event reports involving benzocaine sprays together with symptoms that probably indicated methemoglobinemia in the patients.  It is important to note also that these cases were received over a period of many years and this is an uncommon adverse event.   The FDA is continuing to review all available safety information for these affected products.

¹ In addition to benzocaine, Cetacaine® also contains butyl aminobenzoate and tetracaine as active ingredients.