Septocaine

Articaine and epinephrine are anesthetics (numbing medicines). They work by blocking nerve signals in your body.

Articaine and epinephrine is a combination medicine used to numb your mouth for a dental procedure.

Articaine and epinephrine may also be used for purposes not listed in this medication guide.

You should not receive this medicine if you are allergic to any type of numbing medicine.

To make sure articaine and epinephrine is safe for you, tell your doctor if you have:

• a heart rhythm disorder;

• low or high blood pressure;

• asthma or a sulfite allergy; or

• a history of seizures.

FDA pregnancy category C. It is not known whether articaine and epinephrine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether articaine and epinephrine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Since articaine and epinephrine is given as needed before a dental procedure, you are not likely to be on a dosing schedule.

Approximately 5–10% of available articaine is metabolized by CYP enzymes.1 3

Specific Drugs

Septocaine is contraindicated in patients who are hypersensitive to products containing sulfites. Products containing sulfites may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people [see Warnings and Precautions (5.5)].

Mechanism of Action

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

Pharmacodynamics

Clinically, the order of loss of nerve function is as follows: (1) pain; (2) temperature; (3) touch; (4) proprioception; and (5) skeletal muscle tone.

The onset of anesthesia has been shown to be within 1 to 9 minutes of injection of Septocaine®. Complete anesthesia lasts approximately 1 hour for infiltrations and up to approximately 2 hours for nerve block.

Administration of Septocaine® results in a 3- to 5-fold 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 [see Warnings and Precautions (5.1)].

Pharmacokinetics

Absorption: Following dental injection by the submucosal route of an articaine solution containing epinephrine 1:200,000, 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. Following intraoral administration of a near maximum dose of 476 mg, articaine reaches peak blood concentrations of 2037 and 2145 ng/mL for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively, approximately 22 minutes post-dose.

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 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: At the dose of 476 mg of articaine, the elimination half-life was 43.8 minutes and 44.4 minutes for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively. 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: No studies have been performed to evaluate the pharmacokinetics of Septocaine® injection in pediatric subjects. There is insufficient information to determine whether the pharmacokinetics of Septocaine® injection differs by race.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to evaluate the carcinogenic potential of articaine HCl in animals have not been conducted. Five standard mutagenicity tests, including three in vitro tests (the nonmammalian Ames test, the mammalian Chinese hamster ovary chromosomal aberration test, and a mammalian gene mutation test with articaine HCl) and two in vivo mouse micronucleus tests (one with articaine and epinephrine 1:100,000 and one with articaine HCl alone) showed no mutagenic effects.

No effects on male or female fertility were observed in rats for articaine and epinephrine 1:100,000 administered subcutaneously in doses up to 80 mg/kg/day (approximately 2 times the MRHD based on body surface area).

Kaplan, EL, editor. Cardiovascular disease in dental practice. Dallas; American Heart Association; 1986.

Septocaine® (articaine HCl and epinephrine) Injection is available in 1.7 mL single use glass cartridges, packaged in boxes of 50 cartridges in the following two strengths:

• Septocaine® containing articaine HCl 4% (40 mg/mL) and epinephrine 1:200,000 (as epinephrine bitartrate 0.009 mg/mL) (NDC 0362-9048-02)
• Septocaine® containing articaine HCl 4% (40 mg/mL) and epinephrine 1:100,000 (as epinephrine bitartrate 0.018 mg/mL) (NDC 0362-9049-02)

Storage and Handling

Store at controlled room temperature 25°C (77°F) with brief excursions permitted between 15° and 30°C (59°F-86°F) [see USP Controlled Room Temperature]. Protect from light. Do Not Freeze.

For chemical disinfection of the carpule, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of isopropyl (rubbing) alcohol, as well as solutions of ethyl alcohol not of U.S.P. grade, contain denaturants that are injurious to rubber and therefore are not to be used.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

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 Septocaine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.