Articaine and epinephrine

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include extreme drowsiness, fainting, seizure (convulsions), shallow breathing, or slow heart rate.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Do not eat while your mouth feels numb. You may bite your tongue.
• If you are 65 or older, use articaine and epinephrine with care. You could have more side effects.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Complete anesthesia: ~1 hour (infiltration); ~2 hours (nerve block)

Half-Life Elimination

Articaine/epinephrine: 43.8 to 44.4 minutes

Dental anesthesia: Local, infiltrative, or conductive anesthesia in both simple and complex dental procedures

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

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.

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

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.

Applies to articaine / epinephrine: injectable solution

Other

Other side effects including pain (up to 13%), headache (up to 5%), positive blood aspiration into syringe (3.2%), swelling (2.7%), face edema (1%), infection (1%), neck pain, abdominal pain, ear pain, taste perversion, and accidental injury have been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects including nausea and emesis (1.6%), gingivitis (1%), constipation, diarrhea, dyspepsia, glossitis, gum hemorrhage, mouth ulceration, nausea, stomatitis, tongue edema, tooth disorder, and vomiting have been reported.[Ref]

Musculoskeletal

Musculoskeletal side effects including trismus (1.6%), arthralgia, myalgia, back pain, and osteomyelitis have been reported.[Ref]

General

General side effects including sleepiness (1.1%), malaise, and asthenia have been reported.

Nervous system

Nervous system side effects including paresthesia (1%), numbness and tingling (1%), dizziness, dry mouth, facial paralysis, hyperesthesia, increased salivation, nervousness, neuropathy, paresthesia, somnolence, and exacerbation of Kearns-Sayre syndrome have been reported.

Persistent paresthesias of the lips, tongue, and oral tissues have been reported with use of articaine, with slow, incomplete, or no recovery. These events have been reported chiefly following nerve blocks in the mandible and have involved the trigeminal nerve and its branches.[Ref]

Cardiovascular

Cardiovascular side effects including palpitation (1.0%), hemorrhage, migraine, syncope, tachycardia, and elevated blood pressure have been reported.[Ref]

Respiratory

Respiratory side effects including pharyngitis, rhinitis, sinus pain, and sinus congestion have been reported.

Hematologic

Hematologic side effects including ecchymosis and lymphadenopathy have been reported.

Metabolic

Metabolic side effects including edema and thirst have been reported.

Local

Local side effects including injection site pain and a burning
sensation above the injection site have been reported.

Dermatologic

Dermatologic side effects including pruritus and skin disorder have been reported.

Genitourinary

Genitourinary side effects including dysmenorrhea have been reported.

Some side effects of articaine / epinephrine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

4 to 10 years of age:
The quantity to be injected should be determined by the age and weight of the child and the magnitude of the operation.

For children of less than 10 years who have a normal lean body mass and normal body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas. In any case, the maximum dose of 4% articaine should not exceed the equivalent of 7 mg/kg (0.175 mL/kg) or 3.2 mg/lb (0.0795 mL/lb) of body weight.

4 to 16 years of age:
In clinical trials, 61 pediatric patients between the ages of 4 and 16 years received articaine-epinephrine 1:100,000. Among these pediatric patients, doses from 0.76 mg/kg to 5.65 mg/kg (0.9 to 5.1 mL) were administered safely to 51 patients for simple procedures and doses between 0.37 mg/kg and 7.48 mg/kg (0.7 to 3.9 mL) were administered safely to 10 patients for complex procedures. However, there was insufficient exposure to articaine-epinephrine 1:100,000 at doses greater than 7 mg/kg in order to assess its safety in pediatric patients. No unusual adverse events were noted in these patients.

Approximately 13% of these pediatric patients required additional injections of anesthetic for complete anesthesia. Safety and effectiveness in pediatric patients below the age of 4 years have not been established.