Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [for dental use]:
Articadent: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:100,000 (1.7 mL) [contains sodium metabisulfite]
Articadent: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:200,000 (1.7 mL) [contains sodium metabisulfite]
Orabloc: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:100,000 (1.8 mL) [contains sodium metabisulfite]
Orabloc: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:200,000 (1.8 mL) [contains sodium metabisulfite]
Septocaine with epinephrine 1:100,000: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:100,000 (1.7 mL) [contains sodium metabisulfite]
Septocaine with epinephrine 1:200,000: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:200,000 (1.7 mL) [contains sodium metabisulfite]
Zorcaine: Articaine hydrochloride 4% [40 mg/mL] and epinephrine 1:100,000 (1.7 mL) [contains sodium metabisulfite]
Pharmacology
Mechanism of Action
Articaine: Blocks both the initiation and conduction of nerve impulses by increasing the threshold for electrical excitation in the nerve, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential.
Epinephrine: Increases the duration of action of articaine by causing vasoconstriction (via alpha effects) which slows the vascular absorption of articaine.
Pharmacokinetics/Pharmacodynamics
Distribution
Articaine: ~60% to 80%, bound to albumin and gamma globulins.
Metabolism
Articaine: Hepatic via plasma carboxyesterase to articainic acid (inactive)
Excretion
Urine (primarily as metabolites)
Onset of Action
1 to 9 minutes
Time to Peak
Articaine: ~25 minutes (single dose); 48 minutes (3 doses)
Duration of Action
Complete anesthesia: ~1 hour (infiltration); ~2 hours (nerve block)
Half-Life Elimination
Articaine/epinephrine: 43.8 to 44.4 minutes
Use: Labeled Indications
Dental anesthesia: Local, infiltrative, or conductive anesthesia in both simple and complex dental procedures
Contraindications
Sulfite hypersensitivity.
Documentation of allergenic cross-reactivity for local anesthetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to articaine, epinephrine, or any component of the formulation; allergies to dental anesthetics; patients with inflammation and/or sepsis near the proposed injection site, severe shock, paroxysmal tachycardia, frequent arrhythmia, neurological disease, severe hypertension; children <4 years of age; anesthesia of fingers, toes, tip of nose, ears, and penis; narrow-angle glaucoma; severe heart disease, heart block, or known arrhythmias; recent (3 to 6 months) myocardial infarction; recent (3 months) coronary artery bypass surgery; concurrent use of non-cardioselective beta-blockers, tricyclic antidepressants, MAO inhibitors, ergot derivatives, and halothane (or other similar inhalation type drugs); pheochromocytoma; thyrotoxicosis; severe hepatic/renal insufficiency; bronchial asthma; intravascular use.
Dosage and Administration
Dosing: Adult
Dental anesthesia: Submucosal infiltration and/or nerve block: Articaine 4%/epinephrine: Note: These dosages are guides only; other dosages may be used; however, do not exceed maximum recommended dose. The actual volumes to be used depend upon a number of factors, such as type and extent of surgical procedure, depth of anesthesia, degree of muscular relaxation, and condition of the patient. In all cases, the smallest dose that will produce the desired result should be given. For most routine dental procedures, epinephrine 1:200,000 is preferred; when more pronounced hemostasis or improved visualization of the surgical field are required, epinephrine 1:100,000 may be used. Dosages should be reduced for patients with cardiac disease and acutely ill and/or debilitated patients:
Infiltration: 0.5 to 2.5 mL; total dose of articaine: 20 to 100 mg; maximum dose of articaine: 7 mg/kg (0.175 mL/kg).
Nerve block: 0.5 to 3.4 mL; total dose of articaine: 20 to 136 mg; maximum dose of articaine: 7 mg/kg (0.175 mL/kg).
Oral surgery: 1 to 5.1 mL; total dose of articaine: 40 to 204 mg; maximum dose of articaine: 7 mg/kg (0.175 mL/kg).
Dosing: Geriatric
Dental anesthesia: Submucosal infiltration and/or nerve block: Articaine 4%/epinephrine: Note: These dosages are guides only; other dosages may be used; however, do not exceed maximum recommended dose. The actual volumes to be used depend upon a number of factors, such as type and extent of surgical procedure, depth of anesthesia, degree of muscular relaxation, and condition of the patient. In all cases, the smallest dose that will produce the desired result should be given. For most routine dental procedures, epinephrine 1:200,000 is preferred; when more pronounced hemostasis or improved visualization of the surgical field are required, epinephrine 1:100,000 may be used. Dosages should be reduced for patients with cardiac disease and acutely ill and/or debilitated patients:
65 to 75 years:
Simple procedures: 0.43 to 4.76 mg/kg of articaine.
Complex procedures: 1.05 to 4.27 mg/kg of articaine.
≥75 years:
Simple procedures: 0.78 to 4.76 mg/kg of articaine.
Complex procedures: 1.12 to 2.17 mg/kg of articaine.
Dosing: Pediatric
Dental anesthesia: Note: The provided dosages are guides only; other dosages may be necessary; however, do not exceed maximum recommended dose. The actual volumes to be used depend upon a number of factors, such as type and extent of surgical procedure, depth of anesthesia, degree of muscular relaxation, and condition of the patient. In all cases, the smallest dose that will produce the desired result should be used. Two concentrations of epinephrine (1:100,000 or 1:200,00) with 4% articaine are available; when more pronounced hemostasis or improved visualization of the surgical field are required, epinephrine 1:100,000 may be used; in clinical trials of pediatric patients 4 to 16 years of age, the 1:100,000 was also used; in adults, the manufacturer recommends epinephrine 1:200,000 for most routine dental procedures. Dosages should be reduced for patients with cardiac disease and acutely ill and/or debilitated patients. Dosing presented in variable unit (mg/kg, mg, mL/kg, and mL); use extra precaution to verify dosing units.
Children ≥4 years and Adolescents ≤16 years: Submucosal infiltration and/or nerve block: Articaine 4%/epinephrine: Injection:
Simple procedures: Reported range: 0.76 to 5.65 mg/kg of articaine; maximum articaine dose: 7 mg/kg (0.175 mL/kg of 4% solution)
Complex procedures: 0.37 to 7 mg/kg of articaine; maximum articaine dose: 7 mg/kg (0.175 mL/kg of 4% solution)
Adolescents ≥17 years: Submucosal infiltration and/or nerve block: Articaine 4%/epinephrine: Injection:
Infiltration: 0.5 to 2.5 mL (total articaine dose: 20 to 100 mg); not to exceed 7 mg/kg (0.175 mL/kg of 4% solution) of articaine
Nerve block: 0.5 to 3.4 mL (total articaine dose: 20 to 136 mg); not to exceed 7 mg/kg (0.175 mL/kg of 4% solution) of articaine
Oral surgery: 1 to 5.1 mL (total articaine dose: 40 to 204 mg); not to exceed 7 mg/kg (0.175 mL/kg of 4% solution) of articaine
Administration
For submucosal infiltration and/or nerve block injection. Avoid intravascular injection. Aspirate the syringe after tissue penetration and before injection to minimize chance of direct vascular injection.
Storage
Store at 25°C (77°F) with brief excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Do not freeze.
Drug Interactions
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Benperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy
Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification
Beta-Blockers (Beta1 Selective): May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypertensive effect of EPINEPHrine (Systemic). Exceptions: Arotinolol; Carvedilol; Labetalol. Monitor therapy
Beta-Blockers (with Alpha-Blocking Properties): May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy
Blonanserin: May diminish the therapeutic effect of EPINEPHrine (Systemic). Avoid combination
Bretylium: May enhance the therapeutic effect of Alpha-/Beta-Agonists (Direct-Acting). Monitor therapy
Bromperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Avoid combination
Bupivacaine (Liposomal): Local Anesthetics may enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine, but the optimal duration of dose separation for other local anesthetics is unknown Avoid combination
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy
Chloroprocaine: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Monitor therapy
CloZAPine: May diminish the therapeutic effect of Alpha-/Beta-Agonists. Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy
Ergot Derivatives: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy
Hyaluronidase: May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Consider therapy modification
Inhalational Anesthetics: May enhance the arrhythmogenic effect of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Consider therapy modification
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification
Lurasidone: EPINEPHrine (Systemic) may enhance the hypotensive effect of Lurasidone. Avoid combination
Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Promethazine: May diminish the vasoconstricting effect of EPINEPHrine (Systemic). Management: When vasoconstrictive effects are desired in patients receiving promethazine, consider alternatives to epinephrine. Consider use of norepinephrine or phenylephrine, and avoid epinephrine, when treating hypotension associated with promethazine overdose. Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Consider therapy modification
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy
Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Consider therapy modification
Adverse Reactions
Frequency not always defined.
Adverse reactions are characteristic of those associated with other amide-type local anesthetics; adverse reactions to this group of drugs may also result from excessive plasma levels which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.
Cardiovascular: Facial edema (1%), cardiac arrhythmia, cardiac insufficiency
Central nervous system: Pain (13%), headache (4%), paresthesia (1%), seizure
Gastrointestinal: Gingivitis (1%)
Hypersensitivity: Hypersensitivity reaction
Local: Injection site reaction
Respiratory: Asthma
Miscellaneous: Tissue necrosis
<1%, postmarketing, and/or case reports: Abdominal pain, accidental injury, arthralgia, back pain, constipation, dermatological disease, diarrhea, dizziness, drowsiness, dysgeusia, dysmenorrhea, dyspepsia, ecchymoses, edema, facial paralysis, gingival hemorrhage, glossitis, hemorrhage, hyperesthesia, increased thirst, lymphadenopathy, malaise, methemoglobinemia, migraine, myalgia, nausea, neck pain, nervousness, neuropathy, oral mucosa ulcer, osteomyelitis, otalgia, pharyngitis, pruritus, rhinitis, sialorrhea, stomatitis, syncope, tachycardia, tongue edema, vomiting, weakness, xerostomia
Warnings/Precautions
Concerns related to adverse effects:
- Local toxicity: Epinephrine may cause local toxicity, including ischemic injury or necrosis.
- Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).
- Systemic toxicity: May occur. Systemic absorption of local anesthetics may produce cardiovascular and/or CNS effects. Toxic blood concentrations of local anesthetics depress cardiac conduction and excitability, which may lead to AV block, ventricular arrhythmias, and cardiac arrest (sometimes resulting in death). In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Small doses of local anesthetics injected into dental blocks may produce adverse reactions similar to systemic toxicity, including confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression; these reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Constantly monitor cardiovascular and respiratory vital signs and patient's state of consciousness carefully following each injection.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with impaired cardiovascular function, including patients with heart block. Use local anesthetics containing a vasoconstrictor with caution in patients with vascular disease; patients with peripheral vascular disease or hypertensive vascular disease may exhibit exaggerated vasoconstrictor response, possibly resulting in ischemic injury or necrosis. Dosages should be reduced for patients with cardiac disease.
- Hepatic impairment: Use with caution in patients with severe hepatic disease (has not been studied).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Acutely-ill/debilitated patients: Administer reduced dosages, commensurate with age and physical condition, to debilitated and/or acutely-ill patients.
- Elderly: Use with caution in the elderly; administer reduced dosages to commensurate with age and physical condition.
- Pediatric: Administer reduced dosages, commensurate with age and physical condition, to pediatric patients.
Dosage form specific issues:
- Sodium metabisulfite: May contain sodium metabisulfite, which may cause allergic-type reactions (including anaphylactic symptoms, and life-threatening or less severe asthmatic episodes) in certain susceptible patients. The overall prevalence of the sulfite sensitivity in the general population is unknown, and is seen more frequently in asthmatic than in nonasthmatic persons.
Other warnings/precautions:
- Administration: Avoid intravascular injection; accidental intravascular injection may be associated with convulsions, followed by CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. Aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
- Appropriate use: To avoid serious adverse effects and high plasma levels, use the lowest dosage resulting in effective anesthesia. Repeated doses may cause significant increases in blood levels due to the possibility of accumulation of the drug or its metabolites. Dosage recommendations should not be exceeded.
- Trained personnel: Health care providers should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.
Monitoring Parameters
Cardiovascular and respiratory vital signs; state of consciousness after each injection; CNS toxicity.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in some animal reproduction studies using this combination. Articaine crosses the placenta (Strasser 1977).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site irritation. Have patient report immediately to prescriber signs of methemoglobinemia (blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath), seizure, difficulty breathing, slow breathing, shallow breathing, abnormal heartbeat, lightheadedness, depression, chest pain, dizziness, passing out, agitation, anxiety, noise or ringing in the ears, mouth numbness or tingling, blurred vision, tremors, fatigue, or confusion (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
