No

Local Anesthetic

Anesthesia agent for infiltration and nerve block anesthesia in clinical dentistry; Septocaine™ is indicated for local, infiltrative, or conductive anesthesia in both simple and complex dental and periodontal procedures

C

Septocaine™ is contraindicated in patients with hypersensitivity to local anesthetics of the amide type or to sodium metabisulfite.

Intravascular injections should be avoided; aspiration should be performed prior to administration of Septocaine™; 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. Accidental intravascular injection may be associated with convulsions, followed by CNS or cardiorespiratory depression and coma, ultimately progressing to respiratory arrest. 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.

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. Septocaine™ should also be used with caution in patients with heart block.

Local anesthetic solutions containing a vasoconstrictor (such as Septocaine™) 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. It should also be used cautiously in patients during or following the administration of a potent general anesthetic agent, since cardiac arrhythmias may occur under these conditions.

Systemic absorption of local anesthetics may produce CNS and 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 A-V 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 and 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.

In vitro studies show that ~5% to 10% of articaine is metabolized by the human liver microsomal P-450 isoenzyme system; however, no studies have been performed in patient with liver dysfunction, and caution should be used in patients with severe hepatic disease. Use with caution in patients with impaired cardiovascular function, since they may be less able to compensate for function changes associated with prolonged A-V conduction produced by these drugs.

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; see Usual Dosage

Adverse reactions to Septocaine™ 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.

Central nervous system: Headache (4%), paresthesia (1%)

Gastrointestinal: Gingivitis (1%)

Miscellaneous: Pain (body as a whole 13%), facial edema (1%)

<1% (adverse and intercurrent events recorded in 1 or more patients in controlled trials, occurring at an overall rate of <1%, and considered clinically significant): Abdominal pain, accidental injury, arthralgia, asthenia, back pain, constipation, diarrhea, dizziness, dry mouth, dysmenorrhea, dyspepsia, ear pain, ecchymosis, edema, facial paralysis, glossitis, gum hemorrhage, hemorrhage, hyperesthesia, increased salivation, injection site pain, lymphadenopathy, malaise, migraine, mouth ulceration, myalgia, nausea, neck pain, nervousness, neuropathy, osteomyelitis, paresthesia, pharyngitis, pruritus, rhinitis, skin disorder, somnolence, stomatitis, syncope, tachycardia, taste perversion, thirst, tongue edema, tooth disorder, vomiting

MAO inhibitors, tricyclic antidepressants: Administration of local anesthetic solutions containing epinephrine may produce severe, prolonged hypertension

Phenothiazines, butyrophenones: May reduce or reverse the pressor effects of epinephrine; concurrent use of these agents should be avoided; in situations when concurrent therapy is necessary, careful patient monitoring is essential

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.

Onset: 1-6 minutes following injection

Duration: Complete anesthesia: ~1 hour

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.

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:

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

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

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

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.

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

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

greater than or equal to 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 greater than or equal to 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.

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

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)

No information available to require special precautions

No effects or complications reported

Injection (Septocaine™): Articaine hydrochloride 4% with epinephrine (as bitartrate) 1:100,000, sodium chloride 1.6 mg/mL, sodium bisulfite 0.5 mg/mL, and sodium hydroxide (to adjust pH to 5.0) (1.7 mL cartridges, in boxes of 50)

Septocaine™ (articaine hydrochloride 4% and epinephrine 1:100,000) is the first FDA approval in 30 years of a new local dental anesthetic providing complete pulpal anesthesia for approximately 1 hour. Chemically, articaine contains both an amide linkage and an ester linkage, making it chemically unique in the class of local anesthetics. Since it contains the ester linkage, articaine HCl is rapidly metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is an inactive product of this metabolism. According to the manufacturer, in vitro studies show that the human liver microsomal P-450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid. The elimination half-life of articaine is about 1.8 hours, and that of articainic acid is about 1.5 hours. Articaine is excreted primarily through urine with 53% to 57% of the administered dose eliminated in the first 24 hours following submucosal administration. Articainic acid is the primary metabolite in urine. A minor metabolite, articainic acid glucuronide, is also excreted in the urine. Articaine constitutes only 2% of the total dose excreted in urine.