Benzocaine is a short-acting local anesthetic of the ester type. It is used for topical anesthesia in a wide variety of clinical situations including mucous membrane anesthesia prior to endoscopic examination or instrumentation, gag reflex suppression, anorectal disorders, and various pain syndromes. It is available in many dosage forms including gels, creams, ointments, lotions, aerosols, and lozenges. In 2006, the Veterans Health Administration announced the decision to stop using benzocaine sprays in procedures that require tube insertion in the larynx or pharynx or in minor surgical procedures performed in these locations; other benzocaine products and benzocaine sprays applied to exterior skin are still allowable. The removal of benzocaine sprays used in the mouth and throat from practice is based on the belief that other topical anesthetics are less likely to cause methemoglobinemia. Further, tube insertion or surgical procedures in the larynx or pharynx might cause similar signs of methemoglobinemia, which may mean that methemoglobinemia may go unrecognized in some cases. Many over-the-counter (OTC) products are available for the temporary relief of dental or oral pain. OTC benzocaine products should not be used for teething pain and are contraindicated in infants and children younger than 2 years of age, due to the risk of methemoglobinemia. These products should also be used sparingly and not applied more frequently than 4 times per day in older pediatric patients and adults. Benzocaine and tetracaine are more likely to cause contact sensitization than are other local anesthetics.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
-Apply using a cotton applicator to the desired area.
Other Topical Formulations
-Aerosol: Shake container gently once or twice each time before using. Spray each area liberally from a distance of about 6 to 12 inches.
-Solution: Apply using a cotton applicator to the desired area.
-Gel: Apply using a cotton applicator to the desired area or to instrument prior to insertion.
Rectal Administration
-Ointment: For external use only. Apply to cleansed affected area.
Otic Administration
-Administer in external ear canal; insert cotton plug into the meatus after instillation.
Other Administration Route(s)
Dental Administration
-Gel: Apply to affected area using clean fingertip or a cotton applicator. For toothache, apply to cavity and to the surrounding gums.
-Liquid: Apply to the affected area using a clean fingertip, cotton, or a cotton applicator.
-Ointment: Apply to cleaned and dried dentures.
-Paste: Dab paste onto affected area using a cotton applicator; do not rub or spread paste to avoid crumbling or grittiness.
Contact dermatitis from benzocaine use can result in pruritus, erythema, edema, pain, rash (unspecified), and urticaria. Angioedema occurs with less frequency, although it requires prompt medical attention. Photosensitivity has rarely been reported in patients receiving topical benzocaine.
Benzocaine, like all local anesthetics, can produce significant CNS and cardiovascular toxicity when high serum concentrations are achieved. This rarely occurs, however, because benzocaine is poorly absorbed. CNS toxicity usually presents with symptoms of CNS stimulation such as anxiety, apprehension, restlessness, nervousness, disorientation, confusion, dizziness, headache, blurred vision, tremor, shivering, and/or seizures. Subsequently, depressive symptoms can occur including drowsiness, coma, and respiratory arrest. In some patients, the symptoms of CNS toxicity can be minor and transient. Adverse cardiovascular effects include myocardial depression; sinus bradycardia, sinus tachycardia, or other cardiac arrhythmias; hypotension or hypertension; cardiovascular collapse; and/or cardiac arrest. These effects typically occur with high plasma drug concentrations but have occurred with smaller doses in rare cases. Severe adverse effects from benzocaine administration should be treated with general supportive physiologic measures such as oxygen therapy, assisted ventilation, and IV fluids. Seizures can be treated with a slow infusion of IV diazepam, although this should be done cautiously because diazepam is also a CNS depressant.
Use of benzocaine can result in methemoglobinemia, which is a rare but serious condition where too much of the hemoglobin in red blood cells becomes unable to bind and carry oxygen. Severe cases of methemoglobinemia can result in death. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Chocolate-brown rather than red blood is characteristic and may indicate methemoglobinemia, but this change is a late sign. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible, and have resuscitation equipment and medications readily available, including methylene blue. Use benzocaine products in the smallest amount possible in order to relieve pain. Over-the-counter (OTC) drug products containing benzocaine should not be used to treat infants and children younger than 2 years. More than 400 cases of benzocaine-associated methemoglobinemia have been reported to the FDA or published in the medical literature since 1971. Of the 119 cases recently evaluated, most were serious and required treatment. Twenty-two cases (18%) occurred in pediatric patients; 11 of these were in patients younger than 2 years. Four of the 119 cases (3%) resulted in death, including 1 infant and 3 adults. Thirty-six cases (30%) had a reported methemoglobinemia concentration of 30% to 55% (normal concentration is 1% to 2%). Seventeen cases (14%) had a reported methemoglobinemia concentration of 55% or more, which is considered life-threatening.
Do not use benzocaine 72 hours before having pancreatic function tests with bentiromide because this could interfere with results.
Prolonged use of topical anesthetics is not recommended. Preparations should not be used for more than 2 days without consulting the physician. Applying topical benzocaine preparations to severely traumatized skin (e.g., skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., after exercise or application of thermal heat wraps or heating pads) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of benzocaine or using an occlusive dressing (skin wraps) can increase benzocaine absorption. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly. and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.
Benzocaine can mask the symptoms of acute otitis media infection and should be used with caution in patients with otic pain syndromes. Do not use in patients who have a tympanic membrane perforation or unexplained ear discharge.
Benzocaine is a local ester anesthetic and should not be used in those with ester local anesthetic hypersensitivity. Also, ester-type local anesthetics such as benzocaine are metabolized to para-aminobenzoic acid (PABA) and should not be used in patients with para-aminobenzoic acid, PABA hypersensitivity. Some preparations contain tartrazine, which can cause allergic reactions and bronchospasm in susceptible individuals. Although the overall incidence of tartrazine dye hypersensitivity is low, it occurs more frequently in patients with aspirin sensitivity. Further, some preparations contain parabens, and cautious use of these preparations in patients with paraben hypersensitivity is warranted. The Kank-A SoftBrush product contains butylparaben, ethylparaben, methylparaben, and propylparaben.
There are no adequate data on the developmental risk associated with benzocaine use during human pregnancy. Animal reproduction studies with benzocaine have not been performed. Use during pregnancy only if the maternal condition justifies the potential fetal risks. An increased risk of congenital anomalies was not demonstrated among the children of 47 women treated with benzocaine during the first 4 lunar months of pregnancy or among the children of 238 women treated any time during pregnancy in the Collaborative Perinatal Project. Based upon these data, the use of benzocaine in early in pregnancy may be associated with a low risk of teratogenic effects in humans.
It is not known whether benzocaine is excreted in human breast milk, however in general, topically applied benzocaine is unlikely to affect the nursing infant if it is applied away from the breast. Benzocaine has been associated with life-threatening cases of methemoglobin; products should be applied and used only as directed and the drug should never be applied to the breast or nipple in order to avoid infant ingestion. Benzocaine was not evaluated by previous American Academy of Pediatrics (AAP) recommendations; however, the recommendations considered lidocaine as usually compatible with breast-feeding.
Geriatric patients and those with hepatic disease; cardiac disease or shock; endocrine diseases such as hyperthyroidism, diabetes mellitus, or Graves' disease; or CNS disease are at an increased risk of developing benzocaine-related adverse effects. Benzocaine use can result in potentially dangerous levels of methemoglobinemia. Patients with reduced oxygenation status may have signs and symptoms of methemoglobinemia at lower serum methemoglobin concentrations than healthy individuals. Patients with breathing problems such as those with asthma, bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), or cardiac disease, tobacco smoking patients, and the elderly are at greater risk for complications related to methemoglobinemia. Patients with certain hereditary defects including G6PD deficiency, hemoglobin-M disease, methemoglobin reductase deficiency, and pyruvate-kinase deficiency may also be at greater risk for developing methemoglobinemia. These patients may have an absence or reduced level of enzymes that help reverse methemoglobinemia. OTC benzocaine products should be used sparingly and only as needed; do not apply more frequently than 4 times per day. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible (methemoglobinemia can cause unreliable readings on standard two-wavelength pulse oximeters), and have resuscitation equipment and medications readily available, including methylene blue. Several factors influence the amount of benzocaine contained in a single spray including manufacturer differences, varying concentrations, length of time actuator is depressed, residual container volume, and orientation of the spray.
Over-the-counter (OTC) oral drug products containing benzocaine should not be used for teething pain and are contraindicated in neonates, infants, and children younger than 2 years. Any potential benefits of using these products to treat teething pain do not outweigh their risks. Use of benzocaine can result in life-threatening and fatal methemoglobinemia. OTC benzocaine products should be used sparingly and only as needed in older children and adolescents; do not apply more frequently than 4 times per day. Signs and symptoms of methemoglobinemia may appear within minutes to 1 to 2 hours after benzocaine exposure and may occur with initial and/or subsequent use. Advise patients to seek immediate medical attention for discoloration (pale, gray, or blue-colored) of skin, lips, or nail beds; shortness of breath; fatigue; confusion; headache; lightheadedness; or rapid heart rate. Health care professionals using local anesthetics during medical procedures should monitor patients closely for methemoglobinemia, use co-oximetry when possible (methemoglobinemia can cause unreliable readings on standard two-wavelength pulse oximeters), and have resuscitation equipment and medications readily available, including methylene blue. Several factors influence the amount of benzocaine contained in a single spray including manufacturer differences, varying concentrations, length of time actuator is depressed, residual container volume, and orientation of the spray.
For mild pain to provide topical anesthesia or local anesthesia:
NOTE: For oral or dental uses, see dental anesthesia.
-for anesthesia of unbroken skin:
Topical dosage (cream, gel, ointment, or solution):
Adults, Adolescents and Children 2 years or older: Apply to affected areas 3 to 4 times daily, or as needed. If condition worsens, or if symptoms persist for more than 7 days or clear up and occur again within a few days, discontinue and consult a physician.
Children younger than 2 years : Safety and efficacy have not been established.
Topical dosage (benzocaine 5% or 20% spray):
Adults, Adolescents and Children 2 years or older: Spray on affected areas 3 to 4 times daily, or as needed. Do not exceed a spray duration of 2 seconds. If condition worsens, or if symptoms persist for more than 7 days or clear up and occur again within a few days, discontinue and consult a physician.
Children younger than 2 years: Safety and efficacy have not been established.
-for pain and pruritus associated with minor skin abrasion, burns, sunburn, insect bites or stings, or minor skin irritations:
Topical dosage (benzocaine 5% or 20% spray):
Adults, Adolescents and Children 2 years or older: Apply gel or use spray on affected area not more than 3 to 4 times daily. If using the spray, do not exceed a spray duration of 2 seconds. If condition worsens, or if symptoms persist for more than 7 days or clear up and occur again within a few days, discontinue and consult a physician.
Children younger than 2 years: Safety and efficacy have not been established.
-for self-medication of rectal pain, especially soreness and/or pruritus associated with hemorrhoids and anorectal inflammation (temporary relief only):
Rectal topical dosage (Americaine Hemorrhoidal):
Adults and Adolescents: When practical, cleanse the affected area with mild soap and warm water and rinse thoroughly. Gently dry by patting or blotting with toilet tissue or a soft cloth before application. Apply to perianal area up to 6 times daily. Medication should not be inserted into the rectum. If condition worsens, or does not improve within 7 days, a physician should be consulted.
Children: Safety and efficacy have not been established.
-for oral mucosal anesthesia to control pain and/or suppress the pharyngeal and tracheal gag reflex; or for local anesthesia of accessible mucous membranes before examination, endoscopy or instrumentation; and to facilitate passage of fiberoptic gastroscopes, laryngoscopes, proctoscopes, and sigmoidoscopes:
Topical dosage (Hurricaine Spray):
Adults and Adolescents: Spray on area for one second. May repeat if necessary. Do not exceed a spray duration of 2 seconds.
Topical dosage (gel or solution):
Adults: Apply 20% gel or topical solution either directly to mucosa or to instrument prior to examination, as needed.
-for topical anesthesia in the external auditory canal to relieve ear pain related to acute otitis media and otitis externa:
Otic dosage:
Adults, Adolescents, and Children: Instill 4 to 5 drops into external ear canal; insert cotton plug. May repeat every 1 to 2 hours as needed. Do not use if there is a perforated eardrum or ear discharge.
For dental anesthesia or temporary relief of dental pain or oral pain:
Local oral dosage (topical cream, gel, paste, or solution):
Adults: Apply dental cream (20%), gel (10% or 20%), paste (20%), or solution (20%) to affected area as needed. Apply a small amount topically with a cotton swab or clean fingertip into cavity and around gums up to 4 times per day.
Children and Adolescents 7 to 17 years: Apply dental cream (20%), gel (10% or 20%), paste (20%), or solution (20%) to affected area as needed. Apply a small amount topically with a cotton swab or clean fingertip into cavity and around gums up to 4 times per day.
-for self-medication of pain associated with aphthous ulcer (i.e., canker sore), dental pain associated with toothache, or minor irritations of the mouth and gums (for temporary relief only):
Local oral dosage (Hurricane Gel, Hurricane Liquid, Orajel Gel, Orajel Maximum Strength Gel, Orajel Maximum Strength Liquid, Orajel Mouth-Aid Liquid, Orajel P.M. Maximum Strength, SensoGARD Canker Sore Relief Gel, Orajel Medicated for Toothache Gel, Orajel Medicated for Toothache and Gum Liquid):
Adults: Apply to affected area using either a cotton swab or fingertip up to 4 times daily or as directed by a physician. For toothaches, apply to affected cavity and around gum surrounding the teeth.
Children and Adolescents 2 to 17 years: Apply to affected area using either a cotton swab or fingertip up to 4 times daily or as directed by a physician. For toothaches, apply to affected cavity and around gum surrounding the teeth.
Local oral dosage (CankerMelts tablets):
Adults: Affix 1 tablet in the mouth opposite or adjacent to the sore every 2 hours as needed.
Children and Adolescents 5 to 17 years: Affix 1 tablet in the mouth opposite or adjacent to the sore every 2 hours as needed.
-for self-medication of pain and discomfort of irritations caused by dentures or orthodontic appliances (for temporary relief only):
Local oral dosage (Benzodent Cream, Orajel Denture, Orajel Denture Maximum Strength):
Adults: Clean and dry dentures or orthodontic appliance. Apply directly to the gums or to the denture surface that comes in contact with the affected area of the gum. Wait a few seconds, then reinsert dentures or orthodontic appliance. Use up to 4 times a day or as directed by a dentist. Do not use for more than 7 days. Regular denture adhesives may be used with these product.
Local oral dosage (CankerMelts tablets):
Adults: Affix 1 tablet in the mouth opposite or adjacent to the sore every 2 hours as needed.
Children and Adolescents 5 to 17 years: Affix 1 tablet in the mouth opposite or adjacent to the sore every 2 hours as needed.
Maximum Dosage Limits:
-Adults
The maximum dosage is dependent on route of administration and indication for therapy.
-Geriatric
The maximum dosage is dependent on route of administration and indication for therapy.
-Adolescents
The maximum dosage is dependent on route of administration and indication for therapy.
-Children
2 to 12 years: The maximum dosage is dependent on route of administration and indication for therapy.
1 year: OTC benzocaine products are contraindicated.
-Infants
OTC benzocaine products are contraindicated.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adapalene; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Articaine; Epinephrine: (Moderate) Use articaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzocaine; Butamben; Tetracaine: (Moderate) Use tetracaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Clindamycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Erythromycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzoyl Peroxide; Sulfur: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Bupivacaine Liposomal: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use benzocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Calamine; Pramoxine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Ceftriaxone: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Chloroprocaine: (Moderate) Use chloroprocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Clindamycin; Adapalene; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Dapsone: (Moderate) Coadministration of dapsone with benzocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Dibucaine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Ethyl Chloride: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Hydrocortisone; Pramoxine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Isosorbide Dinitrate, ISDN: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Isosorbide Mononitrate: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as benzocaine. Concomitant use of benzocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lidocaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Tetracaine: (Moderate) Use tetracaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Mafenide: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Menthol; Pramoxine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Mepivacaine: (Moderate) Use mepivacaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitrates: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Nitroglycerin: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as benzocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as benzocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Pramoxine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Pramoxine; Zinc Acetate: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
Ropivacaine: (Moderate) Use ropivacaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfadiazine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Sulfasalazine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Sulfonamides: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides. Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Tetracaine: (Moderate) Use tetracaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tretinoin; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Like all local anesthetics, benzocaine causes a reversible blockade of nerve conduction by decreasing nerve membrane permeability to sodium. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Clinically, loss of function occurs as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying the anesthetic topically to the area to be anesthetized.
Benzocaine is applied topically. Benzocaine is metabolized hepatically. Metabolites are renally excreted.
-Route-Specific Pharmacokinetics
Topical Route
Benzocaine is minimally absorbed after topical administration. Systemic absorption is favored by broken skin or mucosa. Onset of action is rapid with initial effects obtained in about 1 minute and action lasting about 15-20 minutes.