Clinical Pharmacology
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Product Characteristics
OraVerse® (phentolamine mesylate) is a clear, colorless, sterile, nonpyrogenic, isotonic, preservative-free solution. Each 1.8 mL cartridge contains 0.4 mg phentolamine mesylate.
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. The lidocaine concentration increased after OraVerse injection, which suggests that OraVerse promotes clearance of lidocaine from oral tissue into systemic circulation.
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). 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.
OraVerse is indicated for use in adults and children 6 years of age or older and weighing at least 33 lbs.
Important Safety Information
Following parenteral use of phentolamine at doses between 5 and 15 times higher than the recommended dose of OraVerse (phentolamine mesylate), myocardial infarction and cerebrovascular spasm and occlusion have been reported, usually in association with marked hypotensive episodes producing shock-like states. Although such effects are uncommon with OraVerse, clinicians should be alert to the signs and symptoms of tachycardia, bradycardia, and cardiac arrhythmias, particularly in patients with a history of cardiovascular disease, as these symptoms may occur with the use of phentolamine or other alpha-adrenergic blocking agents. See full prescribing information for details.
