Managed Care

 

OraVerse Helps You Lose That Numbing Feeling

MANAGED CARE September 2008. © MediMedia USA
Tomorrow's Medicine

OraVerse Helps You Lose That Numbing Feeling

A common gripe with oral anesthetics is the amount of time it takes for them to wear off
Thomas Morrow, MD
MANAGED CARE September 2008. ©MediMedia USA

A common gripe with oral anesthetics is the amount of time it takes for them to wear off

Thomas Morrow, MD

Few of the products previously described in Tomorrow’s Medicine will ever be used personally by the readers, as most are for rare conditions. But most of us will find phentolamine mesylate (OraVerse) of interest, and many will eventually, however reluctantly, personally experience its benefits.

Most of us will at some time in our life experience the pure ecstasy of the dentist’s drill. Although dental procedures are psychologically painful, they are seldom physically painful because of the relative ease and comfort of the application of dental soft-tissue anesthetics. Typically, the dentist will apply a topical anesthetic, then inject a combination of epinephrine mixed with articaine, lidocaine, or a mixture of prilocaine or levonordefrin with mepivicaine. The caine anesthetics work by blocking neurotransmission. The premixed alpha-adrenergic agonist (either epinephrine or levonordefrin) provides a longer lasting and more profound level of anesthesia to the local tissue.

However, the combination of the anesthetic with the vasoconstrictor comes with a cost: persistent numbness of the cheek, tongue, and lips — something most of us dread. This prolonged numbness interferes with talking, eating, and drinking and for many (including the author) is considered worse than the procedure itself.

Because vasoconstriction, at least in theory, causes delayed clearing of the anesthetic, a reversal of the vasoconstriction was thought to be, and now has been proven to be, an effective approach to shortening the duration of anesthesia. OraVerse, an old and proven drug that is a nonselective alpha-adrenergic blocking agent, has been available in the United States since 1952. It has been shown to reduce the mean duration of lip anesthesia as compared to placebo.

Two studies

Two double-blind randomized multicenter studies were performed to prove that people undergoing routine dental procedures would experience a shortened duration of soft-tissue anesthesia after a local injection of phentolamine mesylate. The first study consisted of 122 otherwise healthy people from 10 to 65 years old undergoing mandibular care. The second study consisted of 120 patients undergoing maxillary care.

The dental procedures consisted of routine periodontal maintenance, restorative procedures, or repairing single crown. All participants received one or two cartridges of a premixed local anesthetic/vasoconstrictor before the dental treatment. At the conclusion of the dental procedure, 1.8 ml of study drug containing 0.4 mg phentolamine mesylate or placebo was injected per cartridge of local anesthetic used.

In both studies, the primary endpoint was time to normal lip sensation as measured by patient-reported response to palpation. The secondary endpoints included patient’s perception of altered function, sensation, appearance, and actual functional deficits in smiling, speaking, drinking, and drooling as assessed by both the patient and an observer blinded to the treatment.

In the mandibular study, the time to recovery of tongue sensation was also a secondary endpoint. Patients were stratified by type and amount of anesthetic administered.

OraVerse reduced the median time to recovery of normal sensation in the lower lip by 85 minutes (55 percent improvement) compared to control. The medial time to recovery of normal sensation in the upper lip was reduced by 83 minutes (62 percent improvement). In the mandibular study, OraVerse accelerated the recovery of the perception of normal appearance and function by 60 minutes (40 percent improvement), the recovery of normal function by 60 minutes (50 percent improvement), and the recovery of normal sensation in the tongue by 65 minutes (52 percent improvement).

Return to normal

In maxillary study, the recovery of the perception of normal appearance and function was reduced by 60 minutes (50 percent) and the recovery of normal function was reduced by 45 minutes (43 percent).

A pediatric double-blinded, randomized, multicenter controlled study was conducted in dental patients who had received 2 percent lidocaine with 1:100,000 epinephrine. The study included 152 patients ages 4–11 who received a half-cartridge of local anesthetic if they weighed more than 15 kg but less than 30 kg and one half or one full cartridge if they weighed more than 30 kg.

The median time to normal lip sensation in patients 6–11 years old was reduced by 75 minutes (56 percent). Within one hour after administration of OraVerse, 44 patients (61 percent) reported normal lip sensation while only nine patients (21 percent) in the control group reported normal lip sensation.

OraVerse is now approved by the Food and Drug Administration for the reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and of the associated functional deficits.

OraVerse is not recommended for use in children who are under 6 years old or weigh less than 15 kg.

Dosage ranges from one-half to two cartridges. Each cartridge contains 0.4 mg of phentolamine mesylate in a total volume of 1.7 ml. There are no listed contraindications and the warnings appear to be generally concerning those who have received phentolamine mesylate for hypotensive episodes. Tachycardia and cardiac arrhythmias may occur with the use of phentolamine or other alpha-adrenergic blocking agent, but such effects are uncommon after administration of OraVerse. The only relatively common adverse reaction was injection site pain. OraVerse has not been studied in pregnant women and is category C. It is not known whether OraVerse is excreted in human milk.

Managed care implications

In general, dental coverage has not included therapies considered “not medically necessary” such as whitening treatments or nitrous oxide (commonly used to allay anxiety by those of us who are inclined to request it). OraVerse might in some ways be considered in the same category.

But for some populations, the risk of self harm from not having feeling in the tongue and lips may actually lead to medically necessary requests from dentists. It could be appropriate for patients with marginal mental abilities and other cognition problems.

For the most part, OraVerse is likely to be a self-pay medication, but one which many of us may personally find useful. It is priced by the manufacturer at about $12.50, depending on size of order, which is a small price to pay for the ability to smile, talk and, most of all, not drool, upon returning to the office!

Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 23 years of managed care experience at the payer or health plan level.

The author is a director in the value-based health department at Genentech Inc. During the last three years, before taking the Genentech position, he received honoraria or other financial benefits from: Amgen, Amylin Pharmaceuticals, AstraZeneca, Biogen Idec, Centocor, Galderma, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Novo Nordisk, Pfizer, Procter & Gamble, Q-Med, Sanofi-Aventis, Teva Pharmaceuticals Industries, UCB, and Wyeth. The views expressed in Tomorrow’s Medicine are the author’s alone.

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