Reversal of Soft-Tissue Local Anesthesia With Phentolamine Mesylate in Adolescents and Adults

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ABSTRACT

Background

The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures.

Methods

On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety.

Results

Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups.

Conclusions

PM was efficacious and safe in reducing the duration of local anesthetic– induced soft-tissue numbness and its associated functional deficits.

Clinical Implications

Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.

Section snippets

SUBJECTS, MATERIALS AND METHODS

We conducted two randomized controlled, double-blinded Phase III clinical trials: one involving the mandible and one involving the maxilla. In both studies, we injected local anesthetic on one side (left or right) of the arch before a restorative or periodontal procedure. Both studies were multi-center studies and took place at 18 (mandibular study) and 16 (maxillary study) research centers. To qualify for either study, patients had to be at least 12 years of age, in need of a restorative or

RESULTS

We screened 247 patients for inclusion in the mandibular study. Of the 244 subjects who met the inclusion criteria and were randomized to receive a PM or sham injection, 163 were randomized to receive lidocaine and epinephrine and 81 were assigned to receive articaine and epinephrine, prilocaine and epinephrine or mepivacaine and levonordefrin (Table 1). All 244 randomized subjects reported that their lips still were numb immediately before the injection of the study drug, while only 196

DISCUSSION

We conducted two randomized, double-blinded, controlled, multicenter, Phase III studies to evaluate the efficacy and safety of PM administered as an intraoral submucosal injection to reverse soft-tissue anesthesia after routine mandibular and maxillary dental restorative or periodontal maintenance procedures that required a local anesthetic containing a vasoconstrictor. The results showed a significant reduction of 85.0 minutes (54.8 percent; P < .0001) and 82.5 minutes (62.3 percent; P <

CONCLUSIONS

An injection of PM administered at the same volume and at the same site as a local anesthetic with vasoconstrictor significantly and safely reduced the duration of soft-tissue anesthesia and associated functional deficits in subjects who had undergone routine nonsurgical dental procedures. In subjects for whom a rapid return to normal oral function is desirable and significant postprocedural pain is not anticipated, PM is the first drug available to clinicians that has been shown to accelerate

References (19)

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This study was sponsored by Novalar Pharmaceuticals, San Diego.

Disclosures.Authors. Drs. Rutherford and Rogy and Ms. Navalta are employees of Novalar Pharmaceuticals. Dr. Yagiela is a paid consultant for Novalar Pharmaceuticals. Drs. Hersh, Moore, Papas and Goodson are members of the Clinical Advisory Board for Novalar Pharmaceuticals. In the past five years, Dr. Hersh has served as a consultant for Novocol Pharmaceutical of Canada (Cambridge, Ontario, Canada), a division of the Septodont Group (New Castle, Del.). In the past five years, Dr. Moore has served as medical director, research coordinator or both to pharmaceutical companies marketing local anesthetic products including Dentsply Pharmaceuticals Division (York, Pa.), Kodak Dental Systems (Rochester, N.Y.), Septodont USA (New Castle, Del.) and Novocol Pharmaceutical of Canada regarding the developments of new anesthetics for dentistry. He also has served as a principal investigator or subinvestigator for FDA-required Phase II and Phase III clinical research contracts awarded to the University of Pittsburgh by Wyeth Consumer Healthcare (Philadelphia), Novocol Pharmaceutical of Canada and Novalar Pharmaceuticals. Study group members. Within the past five years, Dr. Boynes has served as a consultant to pharmaceutical companies marketing local anesthetic products including Novocol Pharmaceutical of Canada and Novalar Pharmaceuticals.

The results of the study described in this article were presented at the International Association for Dental Research/Canadian Association for Dental Research/American Association for Dental Research 85th General Session and Exhibition, March 21, 2007, New Orleans.

The following were principal investigators (PI) and subinvestigators for the Soft Tissue Anesthesia Recovery Group: Jeffrey Bennett (PI), DMD, Indiana University School of Dentistry, Indianapolis; Hafsteinn Eggertsson, DDS, MSD, PhD, Indiana University School of Dentistry, Oral Health Research Institute, Indianapolis; Jodie L. Jarrett, RDH, Indiana University School of Dentistry, Oral Health Research Institute; Melissa S. Mau, BA, Indiana University School of Dentistry, Oral Health Research Institute; Paul A. Moore (PI), DMD, PhD, MPH, University of Pittsburgh; Sean G. Boynes, DMD, MS, University of Pittsburgh; Anne L. Lemak, DMD, University of Pittsburgh; Jayme G. Zovko, BS, University of Pittsburgh; Maribeth Krzesinski, DDS, University of Pittsburgh; O. Basil Aboosi, DMD, University of Pittsburgh; Elliot V. Hersh (PI), DMD, MS, PhD, University of Pennsylvania School of Dental Medicine, Philadelphia; Andres Pinto, DMD, MPH, University of Pennsylvania School of Dental Medicine; Stacey A. Secreto, clinical research coordinator, RMA, University of Pennsylvania School of Dental Medicine; Bridget Gallagher, BA, University of Pennsylvania School of Dental Medicine; Athena Papas (PI), DMD, PhD, Tufts University, Boston; Morton Rosenberg, DMD, Tufts University; Mabi Singh, DMD, MS, Tufts University; Nooruddin Sadruddin Pradhan, DMD, MS, Tufts University; Medha Singh, BDS, MS, Tufts University; Ted P. Raybould (PI), DMD, University of Kentucky College of Dentistry, Lexington; John L. Pfail (PI), DDS, Mount Sinai Medical Center, New York City; David V. Valauri, DDS, Mount Sinai Medical Center; Yordanka K. Ivanova, DMD, Mount Sinai Medical Center; Sharon M. Gordon (PI), DDS, MPH, PhD, University of Maryland Dental School, Baltimore; Alfredo Arribas, DDS, MS, University of Maryland Dental School; Vidya Sankar (PI), DMD, MHS, University of Texas Health Sciences Center at San Antonio; Ernest B. Luce, DDS, University of Texas Health Science Center at San Antonio; Ernest E. Valdez, DDS, University of Texas Health Science Center at San Antonio; Noemi C. Gonzales, RDA, University of Texas Health Science Center at San Antonio; Anthony Henegar (PI), DDS, Irving, Texas; Andrea Schreiber (PI), DMD, New York University College of Dentistry, New York City; Kenneth Allen, DDS, MBA, New York University College of Dentistry; James LoPresti, DDS, New York University College of Dentistry; Judith Kreismann, RDH, BA, MS, New York University College of Dentistry; Margaret Andrew, RN, BSN, New York University College of Dentistry; George A. Freer (PI), DDS, Jean Brown Research, Salt Lake City; Scott Kelsey McGavin (PI), DMD, Jean Brown Research; Georgia Blissett, RN, Jean Brown Research; Pauline McCallister, Jean Brown Research; Jodi Smith, RN, Jean Brown Research; Kim Beales, RN, Jean Brown Research; William V. Giannobile (PI), DDS, PhD, University of Michigan, Ann Arbor; Amy S. Kim, DDS, University of Michigan; Mark D. Snyder, DDS, University of Michigan; Paul R. Snow (PI), DMD, private practice, Chandler, Ariz.; Steven Y. Luo (PI), DDS, private practice, Imperial Beach, Calif.; Amanda Robinson, DDS, private practice, Imperial Beach, Calif.; Steffany Peralta, RDA, private practice, Imperial Beach, Calif.; Michelle Hudson, RDA, private practice, Imperial Beach, Calif.; Jacqueline Kleven (PI), DDS, North Hills Medical Research; J. Max Goodson (PI), DDS, PhD, The Forsyth Institute, Boston; Mary Tavares, DMD, The Forsyth Institute; Jennifer Soncini, DMD, The Forsyth Institute; Maria Chvetchkova, RDH, The Forsyth Institute; Christine Roberts, RDH, The Forsyth Institute; Lora Murray, RDH, The Forsyth Institute; Jacyn Stultz, RDH, MS, The Forsyth Institute; Constantinos C. Floros, The Forsyth Institute; Christine M. Hayashi (PI), DDS, MS, private practice, San Jose, Calif.; Indira Torres, RDA, private practice, San Jose, Calif.; Melinda Parisi, BA, private practice, San Jose, Calif.; Jennifer S. Goss, DDS, private practice, San Jose, Calif.; Deborah Shiba, DDS, private practice, San Jose, Calif.

1

Dr. Hersh is a professor and division director of pharmacology, Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th St., Philadelphia, Pa. 19104-6030

2

Dr. Moore is a professor of pharmacology and the chair, Department of Anesthesiology, School of Dental Medicine, University of Pittsburgh.

3

Dr. Papas is a professor, general dentistry and nutrition, and the research director, Department of Oral Medicine, Tufts University School of Dental Medicine, Boston.

4

Dr. Goodson is a senior member of the staff, and the director of Clinical Research, Clinical Research Collaborative, The Forsyth Institute, Boston.

5

Ms. Navalta is senior vice president, Clinical and Regulatory Affairs, Novalar Pharmaceuticals, San Diego.

6

Dr. Rogy is senior director, Clinical Operations and Clinical Development, Novalar Pharmaceuticals, San Diego.

7

Dr. Rutherford is vice president, Clinical Development, Novalar Pharmaceuticals, San Diego.

8

Dr. Yagiela is a professor and the chair, Diagnostic and Surgical Sciences, University of California Los Angeles, School of Dentistry, and a professor of anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles.

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