Gum Medication
FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth
The U.S. Food and Drug Administration (FDA) is warning the public that the use of benzocaine, the main ingredient in over-the-counter (OTC) gels and liquids applied to the gums or mouth to reduce pain, is associated with a rare, but serious condition. This condition is called methemoglobinemia and results in the amount of oxygen carried through the blood stream being greatly reduced. In the most severe cases, methemoglobinemia can result in death.Benzocaine gels and liquids are sold OTC under different brand names such as Anbesol, Hurricaine, Orajel, Baby Orajel, Orabase, and store brands. Benzocaine is also sold in other forms such as lozenges and spray solutions (also see separate Drug Safety Communication on Benzocaine Sprays1). These products are used to relieve pain from a variety of conditions, such as teething, canker sores, and irritation of the mouth and gums.
Methemoglobinemia has been reported with all strengths of benzocaine gels and liquids, including concentrations as low as 7.5%. The cases occurred mainly in children aged two years or younger who were treated with benzocaine gel for teething. People who develop methemoglobinemia may experience pale, gray or blue colored skin, lips, and nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; and rapid heart rate. In some cases, symptoms of methemoglobinemia may not always be evident or attributed to the condition. The signs and symptoms usually appear within minutes to hours of applying benzocaine and may occur with the first application of benzocaine or after additional use. If you or your child has any of these symptoms after taking benzocaine, seek medical attention immediately.
Benzocaine products should not be used on children less than two years of age, except under the advice and supervision of a healthcare professional. Healthcare professionals and consumers are advised to consider the American Academy of Pediatrics’ recommendations for treating teething pain instead of using the benzocaine teething products:1,2
- Give the child a teething ring chilled in the refrigerator.
- Gently rub or massage the child’s gums with your finger to relieve the symptoms of teething in children.
Adult consumers who use benzocaine gels or liquids to relieve pain in the mouth should follow the recommendations in the product label. Consumers should store benzocaine products out of reach of children. FDA encourages consumers to talk to their healthcare professional about using benzocaine.
Additional 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, using the information in the "Contact Us" box at the bottom of the page.
- 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.3, 4
- Report adverse events or medication errors involving benzocaine to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
A search of the FDA’s Adverse Event Reporting System (AERS) database through March 16, 2011 identified 21 cases of methemoglobinemia associated with the use of OTC benzocaine gel or liquid products.
Of the 21 cases, ten cases were categorized as life-threatening, defined as those patients with a reported methemoglobin level greater than 55%. Six cases were categorized as serious, defined as those patients with a reported methemoglobin level of 30% to 55% or who were were administered methylene blue regardless of the level of methemoglobin. There was also one reported death, but it is unclear from the information provided whether the use of benzocaine gel contributed to the outcome. The last four methemoglobinemia cases associated with the use of benzocaine gel products did not provide sufficient information to determine the severity of methemoglobinemia. Methemoglobin levels were reported in 13 of the 21 cases, and were as follows: 4%, 33%, 40.5%, 42.5%, 44.6%, 45%, 46%, 55.5%, 57%, 59.1%, 64%, 69.9%, and 70.4%.
The methemoglobinemia cases generally occurred when using the OTC benzocaine products at home. The cases mainly involved pediatric patients (n=15), most of whom were two years of age or younger (n=11) and were administered benzocaine gel for teething pain. The other six cases occurred in adult patients who applied the benzocaine gel or liquid to relieve toothache.
Not all cases provided a description of the amount of benzocaine administered. Of the 14 cases that provided information regarding the amount of benzocaine administered, there were five cases that suggested the product was used in accordance with the label recommendations and nine cases in which the product was used inappropriately or excessively.
Among the five cases of methemoglobinemia reported following the labeled use of the product, two cases (one life-threatening case in an adult and one serious case in a pediatric patient) occurred following a single administration of benzocaine gel to the oral mucosa. In the pediatric case that occurred following a single exposure to the product, the reporting physician noted that the one year-old patient was found to have “normal methemoglobin reducing capacity.” Three cases described application frequencies that did not exceed the recommendations in the label (i.e., up to four times daily).
Among the nine cases in which the product was used inappropriately or excessively, six cases described unsupervised self-administration or accidental ingestion of the gel by a child and three cases suggested overuse of the product (n=3) where excessive quantities or applications of the products were administered.
The onset of symptoms or diagnosis of methemoglobinemia generally ranged from a few minutes to one or two hours following the application of the benzocaine gel. Symptoms occurred with the first or subsequent applications of benzocaine gel. For the gel and oral liquid methemoglobinemia cases, cyanosis was the most often reported sign that alerted the patients or caregivers to the condition. In particular, reports describe blue discoloration of the lips and nail beds, as well as ashen extremities. Other signs and symptoms reported included irritability, lethargy, difficulty walking, inability to feel hands and feet, and syncope.
FDA will continue to evaluate this safety issue and will take appropriate regulatory actions as warranted.
References
- Markman L. Teething: facts and fiction. Pediatr Rev. 2009;30:e59-64.
- American Academy of Pediatrics. Teething: 4 to 7 Months. Available at: http://www.healthychildren.org/English/ages-stages/baby/teething-tooth-care/pages/Teething-4-to-7-Months.aspx2. Accessed on March 28, 2011.
- Greer FR, Shannon M; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Committee on Environmental Health. Infant methemoglobinemia: the role of dietary nitrate in food and water. Pediatrics. 2005;116:784-6.
- Ash-Bernal R, Wise, R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine. 2004;83:265-73.
Related Information
- FDA Drug Safety Communication: FDA continues to receive reports of a rare, but serious and potentially fatal adverse effect with the use of benzocaine sprays for medical procedures3
- Questions & Answers: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth4
- Public Health Advisory: Benzocaine Sprays marketed under different names, including Hurricaine, Topex, and Cetacaine5
Source : FDA - 7th April 2011
Link to Source
FDA Drug Safety Communication: FDA continues to receive reports of a rare, but serious and potentially fatal adverse effect with the use of benzocaine sprays for medical procedures
The U.S. Food and Drug Administration (FDA) is alerting healthcare professionals that the Agency continues to receive reports of methemoglobinemia, a serious and potentially fatal adverse effect, associated with benzocaine sprays. These sprays are used during medical procedures to numb the mucous membranes of the mouth and throat.Benzocaine sprays are marketed under different brand names such as Hurricaine, Cetacaine, Exactacain, and Topex.
Methemoglobinemia is a rare, but serious condition in which the amount of oxygen carried through the blood stream is greatly reduced. 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. In some cases, symptoms of methemoglobinemia may not always be evident or attributed to the condition. The signs and symptoms usually appear within minutes to hours of using benzocaine. Conditions such as anemia, heart disease, and lung disease (e.g., emphysema) may exacerbate the toxicity of methemoglobinemia.
In 2006, FDA issued a Public Health Advisory1 warning about methemoglobinemia with the use of benzocaine sprays during medical procedures. Since then, FDA has received 72 new cases of methemoglobinemia, including three resulting in death, associated with the use of benzocaine sprays, bringing the total to 319 cases (see Data Summary below).
A review of the cases indicates that the development of methemoglobinemia after treatment with benzocaine sprays may not be related to the amount applied. In many cases, methemoglobinemia was reported following the administration of a single benzocaine spray. In other cases, methemoglobinemia resulted after excessive amounts were applied. The amount of benzocaine contained in a single spray varies across the different products, and depends on the concentration of the solution, the amount of time the actuator is depressed, the residual volume in the can, and the spatial orientation of the can during spraying. Symptoms may appear within minutes to one or two hours after using benzocaine.
FDA is continuing to evaluate the safety of benzocaine (also see separate Drug Safety Communication on Benzocaine Gels and Liquids2), and the Agency will update the public when it has additional information. FDA will take appropriate regulatory actions as warranted.
Additional Information for Patients
- Benzocaine sprays are marketed under different brand names such as Hurricaine, Cetacaine, Exactacain, and Topex.
- Be aware that benzocaine sprays may cause a serious condition where the amount of oxygen carried through the blood stream is greatly reduced (methemoglobinemia).
- Labels of marketed benzocaine sprays are not currently required as of yet to warn about the risk of methemoglobinemia.
- Know how to recognize the signs and symptoms of methemoglobinemia: pale, gray or blue colored skin, lips, and nail beds; headache; lightheadedness; shortness of breath; nausea; fatigue; and rapid heart rate.
- If you or someone you are caring for has any of these symptoms after receiving benzocaine, seek medical attention immediately. Symptoms of methemoglobinemia generally appear within minutes to one or two hours after using benzocaine spray.
- FDA encourages all patients to talk to their healthcare professional if they have concerns about any treatment they are receiving.
- Report side effects or medication errors from the use of benzocaine to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
- Labels of marketed benzocaine sprays are not currently required as of yet to warn about the risk of methemoglobinemia although the use of benzocaine can cause this condition.
- Carefully monitor patients who receive benzocaine sprays for signs of methemoglobinemia during the procedure and for at least two hours post-application. Signs include pale, gray or blue colored skin, lips, and nail beds; shortness of breath; decreased blood oxygen saturation levels; 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.
- Be aware that the development of methemoglobinemia after treatment with benzocaine spray may not be related to the amount applied; methemoglobinemia has been reported to occur following the administration of a single benzocaine spray.
- Be aware that the amount of benzocaine contained in a single spray varies among different manufacturers and depends on the concentration of the solution, the amount of time the actuator is depressed, the residual volume in the can, and the spatial orientation of the can during spraying.
- 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, which will be additive to that formed by benzocaine products.1, 2
- Report adverse events or medication errors involving benzocaine to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
On February 10, 2006, FDA issued a Public Health Advisory3 warning about the risk of methemoglobinemia associated with benzocaine sprays used to locally numb mucous membranes of the mouth and throat for medical procedures. At the same time, the Veterans Health Administration (VHA) announced its decision to stop using benzocaine sprays for these purposes. Since the issuance of the Public Health Advisory in 2006, FDA has received 72 new cases of serious adverse events, including three deaths, associated with methemoglobinemia after the use of benzocaine sprays, bringing the total to 319 cases.
Of the 319 total cases, there were seven cases of death and 32 cases that were categorized as life-threatening, defined as those patients with a reported methemoglobin level greater than 55%. Two hundred and sixteen cases were categorized as serious, defined as those patients with a reported methemoglobin level of 30% to 55% or who were administered methylene blue regardless of the level of methemoglobin. Methemoglobin levels were reported in 227 cases. The values range from 0.3% to 77% (average 35.2%, median 34.5%).
In the cases, topical benzocaine spray was used for medical procedures such as transesophageal echocardiogram, endoscopy, bronchoscopy, intubation, and feeding tube placements.
Not all cases provided a description of the amount of benzocaine administered. Of the 137 cases that provided information regarding the amount of benzocaine administered, 65 cases contained information that suggested overuse of the product. Sixty-two cases reported that methemoglobinemia occurred following the administration of a single application of benzocaine. Very few of these cases reported the duration of the spray, but those that did indicated the duration of the spray was one second or less.
Seventy-three cases described the timeframe in which the symptoms of methemoglobinemia occurred or methemoglobinemia was diagnosed. The onset of symptoms or diagnosis of methemoglobinemia ranged from a few minutes to days following the application of the benzocaine spray, with most cases diagnosed within one to two hours (n=55). Because the cases of methemoglobinemia generally occurred while the patients were sedated for a procedure, symptoms experienced by the patients were generally not reported. Most commonly, the signs that alerted healthcare professionals to the patients’ condition included increased respiratory rate, shortness of breath, decreased blood oxygen saturation levels, and changes in the patients’ physical appearance (“ashen,” “cyanotic,” “dusky,” and “bluish”). In particular, many cases noted the bluish appearance of the lips. These signs persisted despite treatment with 100% oxygen supplementation. Additionally, many reports noted that when the blood sample was drawn, the blood appeared “dark in color” or “chocolate-brown.”
FDA will continue to evaluate this safety issue and will take appropriate regulatory actions as warranted.
References
- Greer FR, Shannon M; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Committee on Environmental Health. Infant methemoglobinemia: the role of dietary nitrate in food and water. Pediatrics. 2005;116:784-6.
- Ash-Bernal R, Wise, R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine. 2004;83:265-73.
Related Information
- FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth4
- Questions & Answers: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth 5
- Public Health Advisory: Benzocaine Sprays marketed under different names, including Hurricaine, Topex, and Cetacaine6
Source : FDA 7th April 2011
Link to Source