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Septocaine (Articaine Hydrochloride / Epinephrine Bitartrate Subcutaneous) - Description and Clinical Pharmacology

 
 



Septocaine®
(articaine hydrochloride 4% (40 mg/mL)
with epinephrine 1:100,000 injection)

For Infiltration and Nerve Block Anesthesia

DESCRIPTION

Septocaine® injection is a sterile, aqueous solution that contains articaine HCl 4% (40mg/mL) with epinephrine bitartrate in a 1:100,000 strength. Articaine HCl is a local anesthetic, which is chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the molecular and structural formulae are displayed below:

Articaine HCl has a partition coefficient in n-octanol/ Soerensen buffer (pH: 7.35) of 17 and a pKa of 7.8.

Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor that is added to articaine HCl in a concentration of 1:100,000 as the free base. It has a molecular weight of 333.3. The molecular and structural formulae are displayed below:

Septocaine® contains articaine HCl (40mg/mL), epinephrine as bitartrate (1:100,000), sodium chloride (1.6 mg/mL), and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted to 5.0 with sodium hydroxide.

CLINICAL PHARMACOLOGY

Pharmacokinetics

Absorption

Following dental injection by the submucosal route of an articaine solution containing 1:200,000 epinephrine, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses. Peak plasma levels of articaine achieved after 68 and 204 mg doses are 385 and 900 ng/mL, respectively.

Distribution

Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γ-globulins at 37°C in vitro.

Metabolism

Articaine HCl is rapidly metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive. In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid.

Excretion

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 - 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 urine. Articaine constitutes only 2% of the total dose excreted in urine.

Special populations

Effect of Age

No studies have been performed to evaluate the pharmacokinetics of Septocaine® injection in geriatric or pediatric subjects.

Race

There is insufficient information to determine whether the pharmacokinetics of Septocaine® injection differs by race.

Renal and Hepatic Insufficiency

No studies have been performed with Septocaine® injection in patients with renal or hepatic dysfunction.

Pharmacodynamics

Mechanism of action

Articaine HCl is a member of the amino amide class of local anesthetics. 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. Epinephrine is a vasoconstrictor added to articaine HCl to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.

The onset of anesthesia following administration of Septocaine® has been shown to be within 1 to 6 minutes of injection. Complete anesthesia lasts approximately 1 hour.

Administration of articaine HCl with epinephrine results in a 3- to 5-fold increase in plasma epinephrine concentrations compared to baseline; however, in heathly 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 (See WARNINGS).

CLINICAL TRIALS

Three randomized, double-blind, active-controlled studies were designed to evaluate effectiveness of Septocaine® as a dental anesthetic. A total of 882 patients received Septocaine®. Of these, 7% were between 4 and 16 years old, 87% were between 17 and 65 years old, and 6% were at least 65 years old. In addition, 53% of patients were female and 47% were male, with a racial/ethnic distribution of 73% white, 11% Hispanic, 8% black, 5% Asian, and 3%"other" races/ ethnicities. These patients underwent simple dental procedures such as single uncomplicated extractions, routine operative procedures, single apical resections, and single crown procedures, and complex dental procedures such as multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, muco-gingival operations, and other surgical procedures on the bone. Septocaine™ was administered as submucosal infiltration and/or nerve block. Efficacy was measured immediately following the procedure by having the patient and investigator rate the patient's procedural pain using a 10 cm visual analog scale (VAS), in which a score of zero represented no pain, and a score of 10 represented the worst pain imaginable.

Mean patient and investigator VAS pain scores were 0.3 - 0.4 cm for simple procedures and 0.5 - 0.6 cm for complex procedures. These values are summarized in Table 1.

Table 1. Summary of VAS Pain Scores
Septocaine®
(articaine HCl 4% with epinephrine 1:100,000)
Simple proceduresComplex procedures
Number of patients674207
Investigator score (cm)
Mean0.30.5
Median0.00.2
Range0 - 9.00 - 7.3
Patient score (cm)
Mean0.40.6
Median0.00.2
Range0 - 8.00 - 8.7

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