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Articaine and Epinephrine

Pronunciation

(AR ti kane & ep i NEF rin)

Index Terms

  • Epinephrine Bitartrate 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

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.

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.

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: Submucosal infiltration and/or nerve block: Articaine 4%/epinephrine: Children and Adolescents 4 to 16 years: 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:

Simple procedures: 0.76 to 5.65 mg/kg of articaine; maximum dose of articaine: 7 mg/kg (0.175 mL/kg).

Complex procedures: 0.37 to 7 mg/kg of articaine; maximum dose of articaine: 7 mg/kg (0.175 mL/kg).

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution in patients with severe hepatic disease.

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: 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

Cocaine: 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

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:

• Local toxicity: Epinephrine may cause local toxicity, including ischemic injury or necrosis.

• Methemoglobinemia: Local anesthetics containing a vasoconstrictor may cause methemoglobinemia, especially in combination with methemoglobin-inducing agents. Do not use in patients with congenital or idiopathic methemoglobinemia, or in patients who are receiving treatment with methemoglobin-inducing agents.

• 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 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 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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