ATC Class:N01BB08

VA Class:CN204

AHFS Class:

• Local Anesthetics 72:00

Generic Name(s):

• Articaine Hydrochloride

Chemical Name:

• 4-Methyl-3-[[1-oxo-2-(propylamino)propyl]amino]-2-thiopenecarboxylic acid methyl ester monohydrochloride

Molecular Formula:

• C₁₃H₂₀N₂O₃S•HCl

Articaine hydrochloride is an intermediate-acting local anesthetic of the amide type.

Dental Anesthesia

Articaine hydrochloride is used for local, infiltrative, or regional (i.e., nerve block) anesthesia in simple and complex dental and periodontal procedures.1,8 Efficacy and safety of articaine hydrochloride, administered with epinephrine by submucosal infiltration and/or nerve block, were established in several randomized, double-blind studies in adults or children at least 4 years of age undergoing simple (i.e., single uncomplicated extractions, routine operative procedures, single apical resections, single crown procedures) or complex dental procedures (i.e., multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, mucogingival operations, surgical procedures on the bone).1,2 Anesthetic activity was determined by having investigators and patients rate procedural pain using a 10-cm visual analog scale (a score of 0 cm represented no pain and a score of 10 cm represented the worst pain imaginable).1,2 Mean visual analog pain scores were 0.3-0.4 or 0.5-0.6 cm in patients receiving articaine for simple or complex dental procedures, respectively, although individual scores varied widely among patients (range: 0-9 cm).1,2 In a subset of patients 4 to younger than 13 years of age, mean visual analog pain scores were 0.4-0.5 or 0.6-1.1 cm in those receiving articaine for simple or complex procedures, respectively.7

The anesthetic activity of articaine hydrochloride appears to be comparable to that of other local anesthetics (i.e., lidocaine, mepivacaine, prilocaine).2,4,7

General

Articaine hydrochloride may be administered by submucosal infiltration or by nerve block.1 The manufacturer states that articaine hydrochloride 4% with epinephrine 1:100,000 injection should be inspected visually for particulate matter and discoloration prior to administration.1

Dental Anesthesia

Dosage of articaine hydrochloride varies with the type and extent of surgical procedure, the depth of anesthesia, the degree of muscular relaxation, and the condition of the patient.1 The smallest dose required to produce the desired effect should be used.1

The optimum dose for dental anesthesia in adults usually ranges from 20-204 mg of articaine hydrochloride 4% with epinephrine 1:100,000, but individual patients and procedures may require more or less drug.1 The recommended adult dose of articaine hydrochloride with epinephrine is 0.5-2.5 mL (20-100 mg) for infiltration, 0.5-3.4 mL (20-136 mg) for nerve block, or 1-5.1 mL (40-204 mg) for oral surgery, respectively.1 Dosage should be reduced in pediatric patients (4 years of age and older).1 The manufacturer states that the optimum dose in pediatric patients should be determined by the age, weight, and physical condition of the patient and the type and extent of surgical procedure.1

In healthy adults and children, the maximum dose of articaine hydrochloride administered by submucosal infiltration or nerve block should not exceed 7 mg/kg (0.175 mL/kg).1

Special Populations

Dosage should be reduced in geriatric patients (65 years of age and older), patients with cardiac and/or liver disease, debilitated patients, and patients with acute illnesses.1

Contraindications

Known hypersensitivity to local anesthetics of the amide type or to sodium metabisulfite.1,4

Warnings/Precautions

Warnings

Epinephrine Administration

Articaine hydrochloride injection contains epinephrine, which may cause local tissue necrosis or systemic toxicity.1 The manufacturer states that the usual precautions associated with epinephrine administration should be observed.1

CNS and Cardiovascular Effects

Accidental intravascular injection of articaine hydrochloride may result in seizures, CNS or cardiorespiratory depression, coma, and/or respiratory arrest.1

Local anesthetics should be used only by clinicians who are sufficiently knowledgeable in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise from the type of anesthetic block to be used.1 Resuscitative equipment and drugs that may be required for treatment of adverse reactions must be immediately available whenever articaine is used.1

Aspiration should be performed prior to administration of articaine to guard against intravascular injection.1

Sensitivity Reactions

Sulfite Sensitivity

Articaine hydrochloride injection contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.1 The overall prevalence of sulfite sensitivity in the general population is unknown;1 however, such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.1

General Precautions

CNS and Cardiovascular Effects

High plasma concentrations of local anesthetics adversely affect the CNS and cardiovascular systems.1

Adverse CNS effects include restlessness, anxiety, tinnitus, lightheadedness, dizziness, disorientation, excitement, blurred vision, tremors, depression, and drowsiness.1,3

Adverse cardiovascular effects such as reduced myocardial contractility, peripheral vasodilation, and depressed cardiac conduction and excitability may result in decreased cardiac output, decreased arterial blood pressure, atrioventricular block, ventricular arrhythmia, cardiac arrest, and, rarely, death.1

Careful monitoring of level of consciousness and cardiovascular and respiratory vital signs is advised after each local anesthetic injection.1

Articaine should be used with caution in patients receiving potent general anesthetic agents, since cardiac arrhythmias may occur in such patients.1

Specific Populations

Pregnancy

Category C.1 (See Users Guide.)

Lactation

Not known whether articaine or its metabolites are distributed into breast milk.1,4 Caution is advised if the drug is administered in nursing women.1

Pediatric Use

Safety and efficacy not established in children younger than 4 years of age.1,4

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment.1 Use with caution in patients with severe hepatic impairment.1

Cardiovascular Disease

Articaine hydrochloride solution contains epinephrine and should be used with caution in patients with cardiovascular disease (e.g., hypertension, peripheral vascular disease) or heart block.1

Common Adverse Effects

Adverse effects occurring in 1% or more of patients include postprocedural pain,1,2,4,7 headache,1,2,4,7 facial edema,1,2,4 gingivitis,1,2,4 paresthesia,1,2,4 and infection.1,2,4

Monoamine Oxidase (MAO) Inhibitors and Tricyclic Antidepressants (TCAs)

Potential pharmacologic interaction (severe, prolonged hypertension) with epinephrine contained in articaine hydrochloride solution.1 Concomitant use with these agents generally should be avoided;1 careful monitoring is advised in patients requiring concomitant therapy.1

Phenothiazines and Butyrophenones

Potential pharmacologic interaction (reduction or reversal of pressor effect of epinephrine).1 Concomitant use with these agents generally should be avoided;1 careful monitoring is advised in patients requiring concomitant therapy.1

Description

Articaine hydrochloride is a local anesthetic of the amide type with an intermediate duration of action.1,2,3,4 The drug is structurally and pharmacologically related to other agents in this class.1,2,3 Articaine hydrochloride is formulated with epinephrine to decrease the drug's rate and extent of systemic absorption and to prolong its duration of action.1,4

Initial onset of anesthesia following administration of articaine hydrochloride with epinephrine for dental anesthesia occurs in about 1-6 minutes, and complete anesthesia persists for approximately 1 hour.(1-48 Average onset of anesthesia following articaine administration appears to be similar to that of prilocaine, 5,6,8 but slightly faster than that of other local anesthetic agents (e.g., lidocaine). 3,5,8

Following submucosal injection and systemic absorption, articaine is rapidly hydrolyzed by plasma carboxyesterase to its inactive metabolite, articainic acid.1,4 Data from in vitro studies indicate that approximately 5-10% of available articaine is metabolized (to articainic acid) in the liver by the cytochrome P-450 (CYP) microsomal enzyme system.1,3 Like other local anesthetic agents, articaine is excreted mainly in urine as inactive metabolites and small amounts of unchanged drug.1,4

Advice to Patients

Importance of advising patients prior to administration of the possibility of temporary loss of sensation and muscle function following infiltration and nerve block injections.1

Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1

Importance of informing clinicians of existing concomitant therapy, including prescription and OTC drugs.1

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. Is is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Septodont, Inc. Septocaine^® (articaine hydrochloride 4% with epinephrine 1:100,000) injection prescribing information. New Castle, DE; 2000 Apr.

2. Malamed SF, Gagnon S, Leblanc D. Efficacy of articaine: a new amide local anesthetic. J Am Dent Assoc . 2000; 131:635-42. [PubMed 10832257]

3. Oertel R, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet . 1997; 33:417-25. [PubMed 9435991]

4. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc . 2001; 132:177-85. [PubMed 11217590]

5. Simon MAM, Gielen MJM, Alberink N et al. Intravenous regional anesthesia with 0.5% articaine, 0.5% lidocaine, or 0.5% prilocaine. Reg Anesth . 1997; 22:29-34. [PubMed 9010944]

6. Pitkanen MT, Xu M, Haasio J et al. Comparison of 0.5% articaine and 0.5% prilocaine in intravenous regional anesthesia of the arm: a cross-over study in volunteers. Reg Anesth Pain . 1999; 24:131-5.

7. Malamed SF, Gagnon S, Leblanc D et al. A comparison between articaine HCl and lidocaine HCl in pediatric dental patients. Pediatr Dent . 2000; 22:307-11. [PubMed 10969438]

8. Septodont Inc., New Castle, DE: Personal communication.