Benzocaine-Induced Methemoglobinemia: A Case Report

Local anesthetics are classified by their chemical structures, with the two major categories being esters and amides (Table 1). The agent of choice depends on the method of administration, the length of time for which the affected areas require local anesthesia, and potential adverse effects. Table 1 General Anesthetic Agents1 Esters include benzocaine (Cepacol, Reckitt Benckiser; Dermoplast, Prestige Brands Holdings; Chloraseptic, Prestige Brands Holdings; HurriCaine, Beutlich Pharmaceuticals; Lanacane, Reckitt Benckiser; Orabase, Colgate-Palmolive Company; Orajel, Church & Dwight; and Zilactin, Blairex Laboratories); chloroprocaine (Nesacaine, APP Pharmaceuticals); procaine (Novocaine, Colgate-Palmolive Company); and tetracaine.1 Amides include bupivacaine (Marcaine, Hospira; Sensorcaine, AstraZeneca); dibucaine (Nupercainal, Nucere Pharma); levobupivacaine (Chirocaine, Purdue Pharma); lidocaine (Dilocaine, Shire; Solarcaine, Bayer; Lidoderm, Endo Pharmaceuticals; and Xylocaine, Fresenius Kabi USA); mepivacaine (Carbocaine, Cooke-Waite; Isocaine, Novocol Pharmaceutical; Polocaine, Novocol Pharmaceutical); prilocaine (Citanest, Dentsply Pharmaceutical); and ropivacaine (Naropin, Fresenius Kabi).1 Some combination products contain both amides and esters; the most commonly used of these agents include lidocaine/prilocaine (Emla, Akorn, Inc.) and benzocaine/tetracaine/butamben (Cetacaine, Cetylite Industries).1 Amides have largely replaced the esters because they produce fewer adverse effects and generally have a longer duration of action.1 Pramoxine (Analpram, Sebela Pharmaceuticals; Itch-X, B. F. Ascher & Company; Pramegel, Pharmaderm; Pramosone, Sebela Pharmaceuticals; Prax, Ferndale Laboratories; and Tronolane, Abbott Laboratories) is a local anesthetic that does not belong to either the amide or ester class.1 Local anesthesia can be achieved by various methods, including topical administration, infiltration, field block, nerve block, and intravenous regional injection. The method by which a local anesthetic is administered aids its effectiveness by delivering the agent directly to the area that is causing or will cause pain. This decreases systemic absorption and related toxic effects. Systemic absorption could produce toxic effects on both the cardiovascular and nervous systems.1 Welcome to the Pharmacovigilance Forum, where we report on interesting adverse drug reactions (ADRs), including drug-induced disease. ADRs are a leading cause of morbidity and mortality. The Institute of Medicine has estimated that 44,000 to 98,000 deaths occur annually from medical errors, with 7,000 due to ADRs. Studies suggest that 6.7% of hospitalized patients have a serious ADR; about 0.5% die as a consequence. ADRs are a significant, preventable public health problem that we can help mitigate through education. Drug approvals in the U.S. continue to grow. In 2015, the Food and Drug Administration (FDA) approved 45 novel drugs—up from an average of about 28 per year from 2006 through 2014. This is a significant increase, especially since many of these approvals involved complex biologic agents. Yet all pharmaceuticals carry a risk of ADRs, whether they are new and improved, generic agents, older brand products, complex biologics, or biosimilars. Publishing ADR cases is a great way to educate others about little-known reactions, unique patient management of a reaction, or interesting presentations of known reactions to a drug or drug class. Each Pharmacovigilance Forum will discuss noteworthy topics related to ADRs in the clinical realm. Every medication has the potential to cause disease, but clinicians are often slow to recognize drug therapy as an etiological factor. I encourage anyone with a potentially interesting case to contact me, to publish ADRs here or elsewhere, and to report ADRs to the FDA MedWatch program. —Michele B. Kaufman