This course was published in the May 2019 issue and expires May 2022. The author has no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.
After reading this course, the participant should be able to:
- Describe common forms of dental topical anesthetics, and clinical considerations when using various formulations.
- Explain the role of the U.S. Food and Drug Administration in overseeing topical anesthetic agents.
- List some of the contraindications for various topical anesthetics used in dental settings.
By way of example, a partial listing of topical anesthetics used for dental procedures includes benzocaine, lidocaine, Cetacaine (Cetylite) and Oraqix (Dentsply Sirona).2 Most common dental topical anesthetics have been approved by the FDA as safe and effective.3 Many topical anesthetics that are used in dentistry are not FDA approved, however, and while these agents are not necessarily unsafe, they should be used with caution because safe dosages and adverse reactions are unknown. Clinicians should refer to the manufacturer’s instructions for FDA-approved topical anesthetics to understand appropriate dosages, safe application methods and possible adverse reactions (Table 1). If the safety facts are not available, clinicians should refer to the FDA website for information on approved drugs.
AGENTS AVAILABLE IN MANY FORMS
Benzocaine is an FDA-approved drug that is available in various forms, concentrations and over-the-counter agents.3 In the 20% concentration, benzocaine gel is the most commonly used topical anesthetic in dentistry, with an onset time of 30 seconds and duration of five to 15 minutes.2 Different forms of benzocaine are available for various uses; these include (but are not limited to) the temporary relief of tooth pain (over-the-counter gel), severe gag reflexes (aerosols), and needle insertion sites (gel).2 Benzocaine is a former pregnancy category C drug, which indicates animal studies have shown an adverse effect on the fetus, and the risk should not be ruled out in pregnant women.4
In 2015, the FDA adopted new rules regarding pregnancy, lactation and reproductive risks to make labels more meaningful to patients and health care providers.5,6 The new FDA pregnancy risk information replaces the former letter categories (A, B, C, D and X), which had been in use since 1979.5,6 The new narrative sections and subsections allow for better patient counseling and informed decision-making for pregnant women who require pharmacological therapies.5,6 The Pregnancy subsection provides information on dosing and potential risks to the developing fetus and pregnancy exposure registry information, which collects and maintains data on the effects of approved drugs used by pregnant women.5,6
The Lactation subsection provides information about drugs that should not be used during breastfeeding, as well as the timing of breastfeeding to reduce infant exposure to the drug.5,6 The Females and Males Reproductive Potential subsection provides information on pregnancy testing, birth control, and the effect of the medication on fertility or pregnancy loss.5,6 Other contraindications for using benzocaine include ester or para-aminobenzoic acid (PABA) allergies and methemoglobinemia.7,8 Clinicians should ask patients about ester or PABA allergies prior to using benzocaine to avoid possible allergic reactions or side effects, such as localized burning, edema, syncopy, weakness or palpitations.2 The higher the concentration of a drug present in a dental topical anesthetic, the higher the rate of penetration.9 Thus, as most topical anesthetics do not have a maximum recommended dose (MRD), it is important to use small dosages. Systemic toxicity can occur from using high-concentration topical drugs, improper application, and/or the failure to identify potential risks and contraindications for use.9
Lidocaine is another FDA-approved topical anesthetic that is available in various concentrations and over-the counter agents.4 The typical onset time for 2% topical lidocaine is three to five minutes, and its duration is 15 minutes; the MRD for 2% lidocaine is 600 mg in adults and 300 mg in children.7,10 When using lidocaine as either a topical or local anesthetic, clinicians should ask patients if they have allergies to amides or any components of the drug product. It is a former pregnancy category B drug, which means caution should be used when administering to a pregnant patient.3 Potential adverse reactions for topical lidocaine include hypersensitivity, with the following possible symptoms: hives, swelling of lips, tongue, pharynx, larynx or anaphylaxis.7
Available in gel, spray and liquid forms, Cetacaine is a combination of three ester topical anesthetics, 2% tetracaine, 14% benzocaine and 2% butamben.11 It is not an FDA-approved drug, therefore, the MRD is unknown — but caution is indicated due to its tetracaine content and rapid absorption.3 Introduced as a safer alternative to cocaine, tetracaine has a longer duration and is five to eight times more potent.12 The onset time is typically 30 seconds, and it has a duration of 30 to 60 minutes.11 According to the manufacturer, safe applications of the liquid form includes a dose of not more than 0.40 ml; however, the manufacturer does not specify weight limits for children or adults.11 Contraindications for the drug include allergies to esters or PABA. Some reported adverse drug reactions include hypersensitivity, contact dermatitis and, rarely, anaphylaxis.11
Oraqix is an amide topical anesthetic utilized in dental therapy. It is a eutectic mixture of local anesthetics (EMLA) consisting of 2.5% lidocaine and 2.5% prilocaine.13 Approved by the FDA for subgingival application,13 it is a liquid-to-gel system that changes from a liquid at room temperature to a gel when placed subgingivally.5 The MRD is five carpules for adults, and it is not recommended for patients under 18 years of age. The onset time is 30 seconds and it has a 20-minute duration subgingivally.3 Contraindications include allergy to amides or any component of the product.14 Possible adverse reactions include edema, abscess, irritation, pain and ulceration.14
ALTERNATIVE TOPICAL AGENTS
While it is common for dental practices to utilize compounded topical anesthetics, safety concerns exist (Table 2). A compounded topical anesthetic mixes pharmaceutical medications in varying ratios to create a customized drug, as indicated by a specific prescription.15 Compared to other types of dental topical anesthetics, compounded agents are typically more potent due to high drug concentrations, which means they may offer longer duration times.15 Tetracaine is a key ingredient of most compounded topical anesthetics and can be highly toxic if misused.12 A chief issue surrounding compounded topical anesthetics is they are neither FDA-regulated nor unregulated. This means the FDA does not ordinarily regulate them, but may decide to regulate certain compounded topicals in response to adverse experiences.16
Because compounded agents can include various FDA-approved drugs, there are infinite possible combinations and concentrations. Available by prescription, compounded agents are meant to be used for an individual patient, and should not be used as an office-wide drug.15 Cases of misuse and serious reactions have occurred with compounded agents, including methemoglobinemia, which has prompted FDA regulatory action.12,17–20
TAC 20 Alternate is a compounded topical gel composed of 20% lidocaine, 4% tetracaine and 2% phenylephrine.13 The drug concentrations used in compounded agents are important to note before using on patients. For example, it contains 20% lidocaine, which is equivalent to 10 times the injectable concentrations. These levels make it more potent than most injectable drugs, thus the need for caution. Phenylephrine, a vasoconstrictor, increases the duration of the drug. In one study, researchers compared the effectiveness of topical 20% benzocaine with TAC 20 Alternate during placement of temporary anchoring devices.21 The success rate for the TAC 20 Alternate was 100%, and the authors reported significantly lower pain levels than with benzocaine, which only had a 29% success rate.21 Because TAC 20 Alternate is not regulated by the FDA, there is no information available regarding safe application, indications, contraindications, MRD or adverse reactions.3
Another compounded dental topical anesthetic, Profound gel is formulated with 10% lidocaine, 10% prilocaine and 4% tetracaine.1 These concentrations are considerably higher than many topical agents. Profound PET or DēpBlu is an improved version and includes 2% phenylephrine and methylcellulose.21 The latter agent provides greater viscosity for easier application.15 This formulation includes both amide and ester drugs, meaning it is contraindicated in patients with ester allergies or methemoglobinemia.
Baddest Topical in Town is another common compounded topical anesthetic. It consists of 12.5% prilocaine, 12.5% tetracaine, 3% lidocaine and 3% phenylephrine.15 This agent provides strong anesthesia due to the high concentration of tetracaine.15 Best Topical Ever is a similar drug combination that includes 12.5% lidocaine, 12.5% tetracaine, and 3% prilocaine.15 Considering they both utilize amides and esters, these drugs are contraindicated in patients who have ester allergies or methemoglobinemia.
Compounded topical agents have a low therapeutic index, which suggests there is a small difference between therapeutic and toxic doses. In light of this, and because packaging for compounded substances is unmetered, inaccurate dosing can easily occur, which can put patients at risk for systemic intoxication.1 Although there is no drug fact information from the FDA on compounded agents, systematic reviews of compounded agents suggest using no more than 2 ml per patient, with an average onset time of three to four minutes, and an average duration of 30 minutes. A surgical suction tip should be used to remove gross amounts of the topical agent.1 Products that contain phenylephrine or some type of vasoconstrictor are usually light-sensitive and have a shelf life of approximately 90 days.15
Clinicians should exercise caution when using compounded topical agents due to the presence of both amides and esters. Lidocaine and prilocaine are common amides used in dentistry, and products containing these drugs are contraindicated in patients with amide allergies specific to these drugs or poor liver function (since amides are metabolized in the liver).7 Prilocaine is also contraindicated in patients who have a high risk of developing methemoglobinemia.7 The most common esters used in dentistry include benzocaine and tetracaine. Drugs and products containing esters are contraindicated in patients with a PABA allergy or atypical pseudocholinesterase activity.1 Considering that PABA is a metabolic by-product of the drug and a potent allergen that can lead to anaphylactic shock, products with high concentrations of an ester should be used with caution.1 Prolonged application of any dental topical anesthetic, whether it is manufactured or compounded, can cause tissue irritation and transitory taste perversion.3
noninjectable topical anesthetic
Kovanaze (St. Renatus) is the first FDA-approved drug that provides pulpal anesthesia without requiring injection.20 It is a nasal spray formulated with 6 mg tetracaine HCl and 0.1 mg oxymetazoline HCl in each 0.2 ml spray.20 This agent is only meant for intranasal use and provides pulpal anesthesia from the second maxillary right premolar to the second maxillary left premolar.20 The drug is administered on the same side nostril as the maxillary teeth on which the procedure is being completed,20 and is intended for use on adults and children weighing 40 kg or more. For children who weigh at least 40 kg, the recommended dose is not more than two sprays (12 mg) at four to five minutes apart. For patients ages 18 or older, the recommended dosage is two sprays at four to five minutes apart. While a third spray can be administered 10 minutes after the second spray if adequate anesthesia is not achieved, no more than three sprays (18 mg) should be used in adults. This agent is contraindicated in patients who have allergies to esters, PABA, oxymetazoline, or other components of the drug. Other contraindications include epitaxis, dysphasia and methemoglobinemia. Some reported adverse reactions include rhinorrhea, nasal congestion, lacrimation, nasal discomfort and oropharyngeal pain.20
It is important for oral health professionals to stay current on common dental topical anesthetic agents. When using FDA-approved topical anesthetics, clinicians are advised to be familiar with correct application techniques, implications for use, contraindications, and risks for adverse reactions. As noted, compounded topical anesthetics are required by law to have a prescription specific to the patient; consequently, these agents are not intended for office-wide use. Clinicians should exercise caution when using compounded agents because the high concentration of drugs may pose toxicity concerns for patients.
When using any anesthetic, providers should ask patients about allergies to esters, amides or any components of the drug. By understanding these aspects of dental topical anesthetics, clinicians can help make dental procedures more comfortable while minimizing any adverse reactions.
- Kravitz ND. The use of compound topical anesthetics: a review. J Am Dent Assoc. 2007;138:1333–1339.
- Lee HS. Recent advances in topical anesthesia. J Dent Anesth Pain Med. 2016;16:237–244.
- U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance Drug Safety Information — FDA’s Communication to the Public. Available at: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072281.pdf. Accessed March 29, 2019.
- U.S. Food and Drug Administration. FDA Approved Drug Products: Xylocaine 2% Jelly. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/08816s032lbl.pdf. Accessed March 29, 2019.
- Drugs.com. FDA Pregnancy Categories. Available at: https://www.drugs.com/pregnancy-categories.html. Accessed March 29, 2019.
- U.S. Food and Drug Administration. Pregnancy and Lactation Labeling (Drugs) Final Rule. Available at: https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/labeling/ucm093307.htm. Accessed March 29, 2019.
- Bassett KB, DiMarco AC, Naughton DK. Local Anesthesia for Dental Professionals. Upper Saddle River, Florida: Pearson Education Inc; 2010;109–128.
- Hieger MA, Afeld JL, Cumpston KL, Wills BK. Topical benzocaine and methemoglobinemia. Am J Ther. 2017;24:596–598.
- Kumar M, Chawla R, Goyal M. Topical anesthesia. J Anaesthesiol Clin Pharmacol. 2015;31:450–456.
- Council on Clinical Affairs, American Academy of Pediatric Dentistry. Guideline on use of local anesthesia for pediatric dental patients. Pediatr Dent. 2015;37:199–205.
- Cetacaine Topical Anesthetics. Available at: https://www.cetylite.com/dental/topical-anesthetics. Accessed March 29, 2019.
- Malamed S. Handbook of Local Anesthesia. 6th ed. St. Louis, Mo: Elsevier Mosby; 2013.
- Kwong TS, Kusnoto B, Viana G, Evans CA, Watanabe K. The effectiveness of Oraqix versus TAC(a) for placement of orthodontic temporary anchorage devices. Angle Orthod. 2015;81:754–759.
- Oraqix. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021451s007lbl.pdf. Accessed March 29, 2019.
- Kravitz ND, Graham JW, Nicozisis JL, Gill J. Compounded topical anesthetics. J Clin Orthod. 2015;49:307–313.
- U.S. Food and Drug Administration. The FDA Modernization Act of 1997. Available at: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDAMA/ucm089179.htm. Accessed March 29, 2019.
- Graham JW. Profound, needle-free anesthesia in orthodontics. J Clin Orthod. 2006;40:723–724.
- U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for FDA Staff and Industry, Marketed Unapproved Drugs — Compliance Policy Guide. Available at: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070290.pdf. Accessed March 29, 2019.
- U.S. Food and Drug Administration. Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm608265.htm. Accessed March 29, 2019.
- Kovanaze. Available at: http://www.kovanaze.com. Accessed March 29, 2019.
- Reznik DS, Jeske AH, Chen JW, English J. Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices. Anesth Prog. 2009;56:81–85.
Featured image by MR_WILKE/E+/GETTY IMAGES PLUS
From Decisions in Dentistry. May 2019;5(5):36–39.