Safety Profile
The safety of OraVerse has been evaluated in 5 clinical trials involving 777 adults, adolescents and children. To date, over 4,500 dentists have purchased OraVerse. The adverse events reported since the introduction of OraVerse have been consistent with those seen in clinical trials.
OraVerse was well tolerated in clinical trials
- No contraindications
- No known drug interactions with OraVerse
- Pregnancy category C – OraVerse has not been tested in pregnant women or nursing mothers.
- Adverse events for OraVerse were comparable to control in clinical trials
Frequency of Adverse Events in Pooled Studies
| Adverse Event* | OraVerse | Control |
| Total (N=418 patients) | Total (N=359 patients) | |
| Post procedural pain | 6% | 6% |
| Injection site pain | 5% | 4% |
| Tachycardia | 5% | 6% |
| Headache | 3% | 4% |
| Bradycardia | 2% | 0.3% |
*Adverse reactions with frequency greater than or equal to 2% in either group.
Pediatric Safety Profile
The safety profile of OraVerse in children is well demonstrated and provides doctors both an age and weight determinant for the use of the product.
OraVerse is not recommended for use in children less than 6 years of age or weighing less than 15 kg (33 lbs).
OraVerse safety was studied in a multicenter, double-blinded, randomized controlled clinical trial with 152 pediatric patients aged 4-11 and in two adult and adolescent trials with patients 12 and over.* Use in pediatric patients less than 3 years of age or <15 kg (33lbs) has not been established. Consistent with adult and adolescent trials, OraVerse was well tolerated among pediatric patients and similar to control for:
- Adverse events
- Pain or post-treatment analgesic use
- Vital signs or oral mucosa assessments
*Tavares M, Goodson JM, Studen-Pavlovich D, and colleagues. Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. JADA 2008;139(8):1095-1104. Copyright ©2008 American Dental Association. All rights reserved. Excerpted by permission.
Frequency of Adverse Events in Pooled Studies
| Adverse Event* | OraVerse | Control |
| In patients 4-11 years | Total (N=96 patients) | Total (N=56 patients) |
| Injection site pain, mild | 2.1% | 0% |
| Injection site pain, moderate | 3.1% | 3.6% |
| Blood pressure diastolic, mild** | 2.1% | 1.8% |
| Blood pressure, mild** | 2.1% | 1.8% |
*Adverse reactions with frequency greater than or equal to 2% in either group. **Decrease, but without clinical impact.
OraVerse Efficacy
Like any new advancement, OraVerse has to meet your standards for efficacy across the board. We’ve dedicated years to studying and understanding the effectiveness of OraVerse. Phentolamine mesylate, the active ingredient in OraVerse, has been used in medical applications since 1952. As you’ll see below, the clinical trials for OraVerse have yielded positive results.
Get your patients’ feeling back faster.
OraVerse is the first and only local anesthesia reversal agent that accelerates the return to normal sensation and function after routine dental procedures where local anesthetic containing a vasoconstrictor was used. In clinical trials, the patients were able to regain normal sensation twice as fast.*
These trials showed that on average, OraVerse patients not only return to normal sensation faster, but they can speak, smile and drink sooner and drooling is minimized.
*Source: Hersh EV, Moore PA, Papas AS and colleagues. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. JADA 2008;139(8):1080-1093. © 2008 American Dental Association. All rights reserved. Excerpted by permission.
Minutes to return of normal sensation
Upper Lip
OraVerse Control (sham injection)
Lower Lip
OraVerse Control (sham injection)
Pediatric Efficacy
OraVerse was studied in a multicenter, double blinded, randomized controlled clinical trial with 152 pediatric patients. For the efficacy evaluation, a subset of 115 patients aged 6-11 that were trainable in the study methods for assessing efficacy was included. In this trial, OraVerse patients recovered lip sensation in 60 minutes (median time) while patients in the control group recovered in 135 minutes (median time).*
Use in pediatric patients less than 3 years of age or <15 kg (33lbs) has not been established. The most common adverse event with OraVerse that was greater than the control group was injection site pain (5% vs. 4%).
*Tavares M, Goodson JM, Studen-Pavlovich D, and colleagues. Reversal of soft-tissue local anesthesia with phentolamine mesylate in pediatric patients. JADA 2008;139(8):1095-1104. Copyright ©2008 American Dental Association. All rights reserved. Excerpted by permission.
Minutes to return of normal sensation (Pediatric Trial)
Upper Lip
OraVerse Control (sham injection)
Lower Lip
OraVerse Control (sham injection)
Clinical Pharmacology
Product Characteristics
OraVerse (phentolamine mesylate) is a clear, colorless, sterile, nonpyrogenic, isotonic, preservative-free solution. Each 1.7mL cartridge contains 0.4 mg phentolamine mesylate.
Pediatrics
A pediatric pharmacokinetic study was conducted with 19 patients between the ages of 3 and 17. Following intraoral submucosal administration of OraVerse, the phentolamine Cmax was higher (approximately 3.5-fold) in children who weighed between 15 and 30 kg (33 and 66 lbs) than in children who weighed more than 30 kg. However, phentolamine AUC was similar between the two groups. The maximum recommended dose of OraVerse for children 6-11 years of age weighing 15 to 30 kg is 1/2 cartridge (0.2 mg). In pediatric patients weighing at least 10 kg (22lbs), the maximum dose of OraVerse recommended is ¼ cartridge (0.1 mg). The pharmacokinetics of OraVerse in adults and in children who weighed more than 30 kg (66 lbs) are similar after intraoral submucosal injection. The pharmacokinetics of OraVerse after administration of more than 1 cartridge (0.4 mg) has not been studied in children.
Mechanism of Action
The mechanism by which OraVerse accelerates reversal of soft-tissue anesthesia and the associated functional deficits is not fully understood. Phentolamine mesylate, the active ingredient in OraVerse, produces an alpha-adrenergic block of relatively short duration resulting in vasodilatation when applied to vascular smooth muscle. In an animal model, OraVerse increased local blood flow in submucosal tissue of the dog when given after an intraoral injection of lidocaine 2% with 1:100,000 epinephrine.
Pharmacokinetics
Following OraVerse administration, phentolamine is 100% available from the submucosal injection site, and peak concentrations are achieved 10 to 20 minutes after injection. Phentolamine systemic exposure increased linearly after 0.8 mg compared with 0.4 mg OraVerse intraoral submucosal injection. The terminal elimination half-life of phentolamine in the blood was approximately 2 to 3 hours. When OraVerse was administered as an intraoral submucosal injection 30 minutes after injection of a local anesthetic, 2%lidocaine HCl with 1:100,000 epinephrine, the lidocaine concentration increased immediately after OraVerse intraoral injection, which suggests that OraVerse promotes clearance of lidocaine from oral tissue into systemic circulation.
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About OraVerse
OraVerse (Phentolamine Mesylate) injection is the first and only local dental anesthesia reversal agent.
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. It accelerates the return to normal sensation and function following restorative and periodontal maintenance procedures. In randomized, controlled clinical trials, the median time to recovery of normal sensation in the upper lip was 50 minutes for OraVerse patients vs 133 minutes for the control and in the lower lip was 70 minutes vs 155 minutes. Use in pediatric patients less than 3 years of age or <15 kg (33lbs) has not been established.
The most common adverse reaction with OraVerse is injection-site pain.
Important Safety Information
Tachycardia, bradycardia, and cardiac arrhythmias may occur with the use of phentolamine or other alpha-adrenergic blocking agents. Although such effects are uncommon with OraVerse (phentolamine mesylate), clinicians should be alert to the signs and symptoms of these events, particularly in patients with a history of cardiovascular disease. Following parenteral use of phentolamine at doses between 5 to 15 times higher than the recommended dose of OraVerse, myocardial infarction, and cerebrovascular spasm and occlusion have been reported, usually in association with marked hypotensive episodes producing shock-like states.
