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Articaine and Epinephrine

Pronunciation

(AR ti kane & ep i NEF rin)

Index Terms

  • Articaine/Epinephrine Bitartrate
  • Epinephrine and Articaine Hydrochloride

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]

Brand Names: U.S.

  • Articadent™
  • Orabloc™
  • Septocaine® with epinephrine 1:100,000
  • Septocaine® with epinephrine 1:200,000
  • Zorcaine™

Pharmacologic Category

  • Local Anesthetic

Pharmacology

Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of the affected nerve fibers. Clinically, the order of loss of nerve function is as follows: 1) pain, 2) temperature, 3) touch, 4) proprioception, and 5) skeletal muscle tone.

Metabolism

Hepatic via plasma carboxyesterase to articainic acid (inactive)

Excretion

Urine (primarily as metabolites)

Onset of Action

1-6 minutes

Duration of Action

Complete anesthesia: ~1 hour

Half-Life Elimination

Articaine: 1.8 hours; Articainic acid: 1.5 hours

Use: Labeled Indications

Local, infiltrative, or conductive anesthesia during simple and complex dental procedures

Contraindications

Hypersensitivity to local anesthetics of the amide type or any component of the formulation

Dosing: Adult

Summary of recommended volumes and concentrations for various types of anesthetic procedures; dosages (administered by submucosal injection and/or nerve block) apply to normal healthy adults:

Infiltration: Injection volume of 4% solution: 0.5-2.5 mL; total dose: 20-100 mg

Nerve block: Injection volume of 4% solution: 0.5-3.4 mL; total dose: 20-136 mg

Oral surgery: Injection volume of 4% solution: 1-5.1 mL; total dose: 40-204 mg

Note: These dosages are guides only; other dosages may be used; however, do not exceed maximum recommended dose

Special populations: The clinician is reminded that these doses serve only as a guide to the amount of anesthetic required for most routine procedures. 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. Dosages should be reduced for pediatric patients, elderly patients, and patients with cardiac and/or liver disease.

Maximum recommended dosages:

Adults (normal, healthy): Submucosal infiltration and/or nerve block: Not to exceed 7 mg/kg (0.175 mL/kg) or 3.2 mg/lb (0.0795 mL/lb) of body weight

The following numbers of dental cartridges (1.7 mL) provide the indicated amounts of articaine hydrochloride 4% and epinephrine 1:100,000:

1 cartridge provides 68 mg articaine HCl (4%) and 0.017 mg vasoconstrictor (epinephrine 1:100,000)

2 cartridges provides 136 mg articaine HCl (4%) and 0.034 mg vasoconstrictor (epinephrine 1:100,000)

3 cartridges provides 204 mg articaine HCl (4%) and 0.051 mg vasoconstrictor (epinephrine 1:100,000)

4 cartridges provides 272 mg articaine HCl (4%) and 0.068 mg vasoconstrictor (epinephrine 1:100,000)

5 cartridges provides 340 mg articaine HCl (4%) and 0.085 mg vasoconstrictor (epinephrine 1:100,000)

6 cartridges provides 408 mg articaine HCl (4%) and 0.102 mg vasoconstrictor (epinephrine 1:100,000)

7 cartridges provides 476 mg articaine HCl (4%) and 0.119 mg vasoconstrictor (epinephrine 1:100,000)

8 cartridges provides 544 mg articaine HCl (4%) and 0.136 mg vasoconstrictor (epinephrine 1:100,000)

The following numbers of dental cartridges (1.7 mL) provide the indicated amounts of articaine hydrochloride 4% and epinephrine 1:200,000:

1 cartridge provides 68 mg articaine HCl (4%) and 0.0085 mg vasoconstrictor (epinephrine 1:200,000)

2 cartridges provides 136 mg articaine HCl (4%) and 0.017 mg vasoconstrictor (epinephrine 1:200,000)

3 cartridges provides 204 mg articaine HCl (4%) and 0.026 mg vasoconstrictor (epinephrine 1:200,000)

4 cartridges provides 272 mg articaine HCl (4%) and 0.034 mg vasoconstrictor (epinephrine 1:200,000)

5 cartridges provides 340 mg articaine HCl (4%) and 0.043 mg vasoconstrictor (epinephrine 1:200,000)

6 cartridges provides 408 mg articaine HCl (4%) and 0.051 mg vasoconstrictor (epinephrine 1:200,000)

7 cartridges provides 476 mg articaine HCl (4%) and 0.060 mg vasoconstrictor (epinephrine 1:200,000)

8 cartridges provides 544 mg articaine HCl (4%) and 0.068 mg vasoconstrictor (epinephrine 1:200,000)

Dosing: Geriatric

Administer smallest dose to produce desired result.

Geriatric patients (dosages in a clinical trial):

65-75 years

Simple procedures: 0.43-4.76 mg/kg (0.9-11.9 mL) was administered safely to 35 patients.

Complex procedures: 1.05-4.27 mg/kg (1.3-6.8 mL) was administered safely to 19 patients.

≥75 years:

Simple procedures: 0.78-4.76 mg/kg (1.3-11.9 mL) was administered safely to 7 patients.

Complex procedures: 1.12-2.17 mg/kg (1.3-5.1 mL) was administered safely to 4 patients.

Note: Approximately 6% of the patients 65-75 years of age (none of the patients ≥75 years of age) required additional injections for complete anesthesia, compared to 11% of the patients 17-65 years of age who required additional injections.

Dosing: Pediatric

Note: Give smallest dose that will produce desired result

Children <4 years: Safety and efficacy have not been established

Children 4-16 years (dosages in a clinical trial of 61 patients):

Simple procedures: 0.76-5.65 mg/kg (0.9-5.1 mL) was administered safely to 51 patients

Complex procedures: 0.37-7.48 mg/kg (0.7-3.9 mL) was administered safely to 10 patients

Note: Approximately 13% of the pediatric patients required additional injections for complete anesthesia

Maximum recommended dosages: Children (use in pediatric patients <4 years is not recommended): Not to exceed 7 mg/kg (0.175 mL/kg) or 3.2 mg/lb (0.0795 mL/lb) of body weight

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied). Use with caution in patients with severe liver disease.

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

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: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification

Blonanserin: 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

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

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

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

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

MAO Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Systemic). 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

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 (Direct-Acting). Management: Avoid, if possible, the use of direct-acting 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% (Limited to important or life-threatening): 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:

• Cardiovascular effects: Systemic absorption of local anesthetics may produce cardiovascular effects. Changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal at blood concentrations produced by therapeutic doses. However, toxic blood concentrations 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. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs should be done following each local anesthetic injection.

• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Treatment is primarily symptomatic and supportive.

• Methemoglobinemia: Has been reported with articaine; may be treated with methylene blue, 1-2 mg/kg IV infused over several minutes.

• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.

• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with impaired cardiovascular function, since they may be less able to compensate for function changes associated with prolonged AV conduction produced by these drugs. Use with caution in patients with heart block.

• Hepatic impairment: Use with caution in patients with severe hepatic disease; in vitro studies show that ∼5% to 10% of articaine is metabolized by the human liver microsomal P450 isoenzyme system; however, no studies have been performed in patient with liver dysfunction.

• Vascular disease: Local anesthetic solutions containing a vasoconstrictor should be used cautiously. Patients with peripheral vascular disease or hypertensive vascular disease may exhibit exaggerated vasoconstrictor response, possibly resulting in ischemic injury or necrosis.

Concurrent drug therapy issues:

• Epinephrine: Contains epinephrine, which can cause local tissue necrosis or systemic toxicity, usual precautions for epinephrine administration should be observed. Administration of articaine HCl with epinephrine results in a three- to fivefold increase in plasma epinephrine concentrations compared to baseline; however, in healthy adults, it does not appear to be associated with marked increases in blood pressure or heart rate, except in the case of accidental intravascular injection.

• General anesthetics: Use with caution in patients during or following the administration of a potent general anesthetic agent, since cardiac arrhythmias may occur under these conditions.

Special populations:

• Pediatric: Safety and efficacy have not been established in children <4 years of age.

Dosage form specific issues:

• Sodium metabisulfite: Products 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: Intravascular injections should be avoided; 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 dosing: To avoid serious adverse effects and high plasma levels, the lowest dosage resulting in effective anesthesia should be administered. Repeated doses may cause significant increases in blood levels with each repeated dose due to the possibility of accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with patient status. Reduced dosages, commensurate with age and physical condition, should be given to debilitated patients, elderly patients, acutely-ill patients, and pediatric patients.

• Dental blocks: Small doses of local anesthetics injected into dental blocks may produce adverse reactions similar to systemic toxicity seen in unintentional intravascular injections at larger doses. Confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving such blocks should be observed constantly with resuscitative equipment and personnel trained in treatment of adverse reactions immediately available. Dosage recommendations should not be exceeded.

• Trained personnel: Dental practitioners and/or clinicians using local anesthetic agents 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.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were 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 shortness of breath, seizures, angina, abnormal heartbeat, severe dizziness, passing out, headache, agitation, anxiety, tinnitus, blurred vision, tremors, fatigue, severe loss of strength and energy, bluish skin, 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 healthcare 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.

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