Generic Name: phentolamine mesylate
Date of Approval: May 9, 2008
Company: Novalar Pharmaceuticals, Inc.
Treatment for: Reversal of Dental Anesthesia
FDA Approves OraVerse
The United States Food and Drug Administration (FDA) has approved OraVerse (phentolamine mesylate) for the reversal of soft-tissue anesthesia and the associated functional deficits resulting from a local dental anesthetic.
The approval of OraVerse for use in adults and children is based on data from several clinical studies, including two Phase 3 studies in adults and adolescents age 12 and older and a Phase 2 pediatric study. The two Phase 3 studies were conducted in 18 centers across the United States, including leading dental schools, clinical research organizations and private clinics. There were 484 dental patients enrolled across the two studies.
In the randomized, double-blinded, controlled Phase 3 studies, following the administration of local anesthetics and completion of the dental procedure, patients were administered either OraVerse or control. OraVerse reduced the median time to recovery of normal sensation in the lower lip (as measured by standardized lip tapping procedures) by 85 minutes compared to control. OraVerse reduced the median time to recovery of normal sensation in the upper lip by 83 minutes. Within one hour after administration of OraVerse, 41% of patients reported normal lower lip sensation as compared to 7% in the control group, and 59% of patients in the OraVerse group reported normal upper lip sensation as compared to 12% in the control group. In both Phase 3 studies, the primary endpoint showed that OraVerse was statistically different compared to control (p<0.0001).
The multi-center, randomized, double-blinded, controlled Phase 2 pediatric study evaluated the safety and efficacy of OraVerse in the reversal of soft tissue anesthesia in patients undergoing dental procedures after receiving local anesthetic. This study enrolled 152 patients: 96 patients in the OraVerse group and 56 patients in the control group. Of the 152 patients enrolled, 115 were trainable in the assessment method: 72 patients in the OraVerse group and 43 patients in the control group. The study assessed the efficacy of OraVerse through the measurement of time to normal lip sensation for those trainable in the assessment. The median time to normal sensation in patients age 6-11 was reduced by 75 minutes for the OraVerse treated group, a 56% acceleration of the time to normal sensation.
In all OraVerse clinical trials, there were no serious adverse events reported and the most common adverse reaction that was greater than control was transient injection site pain. Although tachycardia and cardiac arrhythmia may occur with the parenteral use of alpha-adrenergic blocking agents, such events are uncommon after submucosal administration of OraVerse.
OraVerse (phentolamine mesylate) Injection is the only local anesthetic reversal agent that accelerates the return to normal sensation and function following restorative and periodontal maintenance procedures. OraVerse is indicated for the reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. OraVerse is not recommended for use in children less than six years of age or weighing less than 15 kg (33 lbs).
About Prolonged Soft-Tissue Anesthesia
Prolonged soft-tissue anesthesia is an unnecessary and unwanted side effect of local dental anesthesia, especially in routine, restorative or hygienic dental procedures.
Absorption of the local anesthetic into the cardiovascular system is passive and the local anesthetic remains in and around the nerves in the lips, cheek, and tongue causing the unwanted side effect of lingering numbness.
This numbness can last up to five hours following treatment. This results in difficulty in speaking, eating, and drinking, and prevents patients from returning to their daily activities. Prolonged numbness, especially in children, can result in injury due to accidental biting of the lip and/or tongue.
OraVerse is a novel formulation of phentolamine, an alpha-adrenergic antagonist. The hypothesis for the mechanism of action is that OraVerse acts as a vasodilator and the result is faster diffusion of anesthetic into the cardiovascular system and away from the site, thereby reducing the unwanted side effects of lingering lip and tongue numbness.