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).
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.
Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see WARNINGS, PRECAUTIONS General and ADVERSE REACTIONS).
Management of Local Anesthetic Emergencies
The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.
The first step in the management of convulsions, as well as hypoventilation, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation as needed. The adequacy of the circulation should be assessed. Should convulsions persist despite adequate respiratory support, treatment with appropriate anticonvulsant therapy is indicated. The practitioner should be familiar, prior to the use of local anesthetics, with the use of anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor.
If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.