Benzocaine and the risk of methaemoglobinaemia

HSA would like to inform healthcare professionals of the risk of methaemoglobinaemia associated with the use of benzocaine containing products. Benzocaine is commonly administered orally as lozenges or applied topically as a gel or spray to relieve pain from a variety of conditions such as teething, canker sores, sore throat, irritation of the mouth and gums or during medical procedures to numb mucous membranes of the mouth and throat. There are 7 benzocaine containing products registered locally, namely Dorithricin® throat lozenges, Horf® lozenges, Pharynx® lozenges, Freez-eez® topical anesthetic gel 20% w/w, Topicale® gel 180 mg/g, Hurricaine® gel 20% and Hurricaine® spray 20%.

Signs and symptoms of methemoglobinemia

Methaemoglobinaemia is a rare but serious and potentially fatal condition in which there is a reduction in the oxygen-carrying capacity of the blood. Signs and symptoms (including cyanosis, dyspnoea, lightheadedness, fatigue, decreased blood oxygen saturation levels and tachycardia) usually appear within minutes to hours after benzocaine administration and may occur after first application or following repeated use.

Post market data from the US Food and Drug Administration (FDA)

Despite the issuance of an advisory in 2006, FDA continues to receive reports of new cases of methaemoglobinaemia associated with the use of benzocaine sprays during medical procedures. A review of the cases indicated that methaemoglobinaemia may occur following a single administration of the benzocaine spray and may not be related to the amount applied. Of the 319 cases reported when used with benzocaine sprays, there were seven (2.2%) cases of death, 32 (10%) cases categorized as life-threatening* and 216 (67.7%) cases categorized as serious*. Most of these cases reported were using the topical benzocaine spray for medical procedures such as transesophageal echocardiogram, endoscopy, bronchoscopy, intubation and feeding tube placements.

Methaemoglobinaemia has also been reported with benzocaine gels and liquids, including those with concentrations as low as 7.5%. Of the 21 reports of methaemoglobinaemia associated with the use of benzocaine gel or liquid products, 10 (47.6%) cases were categorized as life-threatening and 6 (28.6%) cases reported as serious. There was also one report of death but it remains unclear if the use of benzocaine gel contributed to the outcome. Most of the cases involved mainly paediatric patients, particularly children aged two years or younger, who were administered benzocaine gel for teething pain. However, it should also be noted that in 9 (42.9%) of the cases, the benzocaine products were used excessively or not in accordance with label recommendations (eg. Unsupervised self-administration or accidental ingestion of the gel by a child).

Advisory

No reports of methaemoglobinaemia associated with use of benzocaine containing products have been received locally. However, healthcare professionals are advised to take note of the following when prescribing or managing patients using benzocaine containing products:

• Benzocaine containing products should not be used on children less than two years of age, except under the advice and supervision of a healthcare professional.

• Benzocaine gels and liquids should be used sparingly and only when needed, but not more than four times a day.

• Discuss signs and symptoms of methaemoglobinaemia with patients prior to prescribing benzocaine products. Advise patients to monitor for signs and symptoms of methaemoglobinaemia when using benzocaine products and to seek medical attention immediately if methaemoglobinaemia is suspected.

• Monitor patients for the signs and symptoms of methaemoglobinaemia,

• Symptoms may appear within minutes to hours after using benzocaine.

• Symptoms may occur with the first or subsequent applications of benzocaine and may not be related to the amount administered.

• Patients who have asthma, bronchitis, emphysema or 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, haemoglobin-M disease, NADH-methaemoglobin reductase (diaphorase 1) deficiency, and pyruvate-kinase deficiency may also be at greater risk of developing methaemoglobinaemia.

• Medications, foods and water containing nitrites and nitrates may also induce methaemoglobin formation in addition to that caused by benzocaine products.

• Healthcare professionals are strongly encouraged to report any adverse reactions suspected to be associated with benzocaine containing products to the Vigilance Branch of HSA._{*Life-threatening cases are those with methaemoglobinaemia levels >55%; serious cases are those with methaemoglobin levels between 30-55%.}

References

1. FDA Drug Safety Communication: Benzocaine Sprays
   http://www.fda.gov/Drugs/DrugSafety/ucm250040.htm

2. FDA Drug Safety Communication: Benzocaine Gels, Liquids
   http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm