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Septocaine (Articaine Hydrochloride / Epinephrine Bitartrate Subcutaneous) - Warnings and Precautions

 
 



WARNINGS

ACCIDENTAL INTRAVASCULAR INJECTION MAY BE ASSOCIATED WITH CONVULSIONS, FOLLOWED BY CENTRAL NERVOUS SYSTEM OR CARDIORESPIRATORY DEPRESSION AND COMA, PROGRESSING ULTIMATELY TO RESPIRATORY ARREST. DENTAL PRACTITIONERS AND/OR CLINICIANS WHO EMPLOY LOCAL ANESTHETIC AGENTS SHOULD BE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF EMERGENCIES THAT MAY ARISE FROM THEIR USE. RESUSCITATIVE EQUIPMENT, OXYGEN, AND OTHER RESUSCITATIVE DRUGS SHOULD BE AVAILABLE FOR IMMEDIATE USE.

Intravascular injections should be avoided. To avoid intravascular injection, aspiration should be performed before Septocaine® is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

Septocaine® contains epinephrine that can cause local tissue necrosis or systemic toxicity. Usual precautions for epinephrine administration should be observed.

Septocaine® contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

PRECAUTIONS

General

Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (See WARNINGS). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of Septocaine® may cause significant increases in blood levels with each repeated dose because of possible accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated patients, elderly patients, acutely ill patients and pediatric patients should be given reduced doses commensurate with their age and physical condition. Septocaine® should also be used with caution in patients with heart block.

Local anesthetic solutions, such as Septocaine®, containing a vasoconstrictor should be used cautiously. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result. Septocaine® should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions.

Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias, and cardiac arrest, sometimes resulting in fatalities. 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 accomplished after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of central nervous system toxicity.

In vitro studies show that about 5% to 10% of articaine is metabolized by the human liver microsomal P450 isoenzyme system. However, because no studies have been performed in patients with liver dysfunction, caution should be used in patients with severe hepatic disease. Septocaine® should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs.

Small doses of local anesthetics injected in dental blocks may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of 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 these blocks should be observed constantly. Resuscitative equipment and personnel for treating adverse reactions should be immediately available.

Dosage recommendations should not be exceeded.

(See DOSAGE and ADMINISTRATION.)

Information for Patients

The patient should be informed in advance of the possibility of temporary loss of sensation and muscle function following infiltration and nerve block injections.

Clinically Significant Drug Interactions

The administration of local anesthetic solutions containing epinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.

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 micronucleous tests (one with Septocaine® and one with articaine HCl alone) showed no mutagenic effects. No effects on male or female fertility were observed in rats for Septocaine® administered subcutaneously in doses up to 80 mg/kg/day (approximately two times the maximum male and female recommended human dose on a mg/m2 basis).

Pregnancy

Teratogenic Effects-Pregnancy Category C

In developmental studies, no embryofetal toxicities were observed when Septocaine® was administered subcutaneously throughout organogenesis at doses up to 40 mg/kg in rabbits and 80 mg/kg in rats (approximately 2 times the maximun recommended human dose on a mg/m2 basis). In rabbits, 80 mg/kg (approximately 4 times the maximun recommended human dose on a mg/m2 basis) did cause fetal death and increase fetal skeletal variations, but these effects may be attributable to the severe maternal toxicity, including seizures, observed at this dose.

When articaine hydrochloride was administered subcutaneously to rats throughout gestation and lactation, 80 mg/kg (approximately 2 times the maximun recommended human dose on a mg/m2 basis) increased the number of stilbirths and adversely affected passive avoidance, a measure of learning, in pups. This dose also produced severe maternal toxicity in some animals. A dose of 40 mg/kg (approximately equal to the maximun recommended human dose on a mg/m2 basis) did not produce these effects. A similar study using Septocaine® (articaine hydrochloride and epinephrine 1:100,000) rather than articaine hydrochloride alone produced maternal toxicity, but no effects on offspring.

There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. Septocaine® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether articaine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Septocaine® is administered to a nursing woman.

Pediatric Use

In clinical trials, 61 pediatric patients between the ages of 4 and 16 years received Septocaine®. 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 Septocaine® at doses greater than 7.00 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. Dosages in pediatric patients should be reduced, commensurate with age, body weight, and physical condition. See DOSAGE AND ADMINISTRATION.

Geriatric Use

In clinical trials, 54 patients between the ages of 65 and 75 years, and 11 patients 75 years and over received Septocaine™. Among all patients between 65 and 75 years, doses from 0.43 mg/kg to 4.76 mg/kg (0.9 to 11.9 mL) were administered safely to 35 patients for simple procedures and doses from 1.05 mg/kg to 4.27 mg/kg (1.3 to 6.8 mL) were administered safely to 19 patients for complex procedures. Among the 11 patients ≥ 75 years old, doses from 0.78 mg/kg to 4.76 mg/kg (1.3 to 11.9 mL) were administered safely to 7 patients for simple procedures and doses of 1.12 mg/kg to 2.17 mg/kg (1.3 to 5.1 mL) were administered to 4 patients for complex procedures.

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Approximately 6% of patients between the ages of 65 and 75 years and none of the 11 patients 75 years of age or older required additional injections of anesthetic for complete anesthesia compared with 11% of patients between 17 and 65 years old who required additional injections.

Page last updated: 2006-12-26

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