Pharmacology Update

New Treatment for Aphthous Ulcers

By William T. Elliott MD, FACP, and James Chan PharmD, PhD

Amlexanox oral paste (apthasol) is a new agent for the treatment of recurrent minor aphthous ulcers. The drug, which has shown antiinflammatory and anti-allergic properties both in vitro and in vivo, is formulated as an oral paste that is applied four times a day to aphthous ulcers. The FDA has approved amlexanox for the treatment of aphthous ulcers in immunocompetent individuals.1

Potential Advantages

Amlexanox has been reported to produce a moderate but statistically significant improvement in time to complete resolution of pain and to complete ulcer healing when compared to no treatment. The difference in median times to complete resolution of pain for amlexanox vs. no treatment was 1.3 days (3.3 days vs 4.6 days). The difference in time to complete healing was 1.6 days (4.8 days vs 6.4 days). This study was performed in a cohort of 452 patients and was statistically significant (P < 0.001). After three days of treatment, 21% of patients treated with amlexanox had complete healing compared to 8% with no treatment. The percent of patients with pain resolution at three days was 44% vs. 20%.

In a placebo-controlled trial using the vehicle as placebo, the differential between amlexanox and vehicle alone was smaller than the differential with no treatment—0.7 days for both resolution of pain (3.4 days vs 4.1 days) and complete ulcer healing (4.9 days vs 5.6 days). These were statistically significant based on a large sample size (n = 938). After four days of treatment, the percentage of patients with complete healing was 37% vs. 27%, and pain resolution was 60% vs. 49%.2 The majority of subjects (81%) presented with a single ulcer with mean size of 4.7-7.8 mm2 and pain scores of 4.1 to 4.7, representing pain with slight to moderate aggravation.

Potential Disadvantages

Amlexanox must be applied four times a day after breakfast, lunch, dinner, and at bedtime. Treatment must be started as soon as possible after symptom onset (48 hours).1,2

Dosing Information

Amlexanox is supplied in a 5% oral paste (5 g). Patients should apply about one-quarter inch of paste onto each ulcer four times a day, preferably following oral hygiene after breakfast, lunch, and dinner. The medication should be used until the ulcer heals. If significant healing or pain reduction has not occurred in 10 days, a physician or dentist should be consulted.


Aphthous ulcers (canker sores or aphthous stomatitis) are self-limiting, recurrent, moderately painful ulcers of the labial and buccal mucosa. About 15-20% of the population develop these ulcers periodically. Ulcers generally heal in 7-10 days and usually do not result in any scarring. The cause of aphthous ulcers is not known, but factors such as trauma, stress, chemical irritation, and hormonal changes in women may contribute to recurrence.2-4

Topical protectants such as Orabase and benzoin tincture have been the mainstays of treatment and are somewhat effective in protecting lesions and providing temporary symptomatic relief. Topical anesthetic/analgesic pastes and gels may also provide temporary pain relief.5

Amlexanox has been shown to produced a modest improvement in healing and pain resolution of minor aphthous ulcers. Compared to the vehicle alone, which may produce the degree of benefit similar to other treatments (e.g., Orabase), the benefit of amlexanox, though statistically significant, was less dramatic. It is not clear if this difference is clinically significant in a real-world setting. There are no comparative studies between these OTC products and amlexanox.

Aphthasol is expected to be available commercially (by prescription) in late September. Cost is not available at this time.


1. Aphthasol Product Information. Block Drug Company, Inc. December 1996.

2. Khandwala A, et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:222-230.

3. Vincent SD, et al. Oral Surg Oral Med Oral Pathol 1992;74:79-86.

4. Antoon JW, et al. J Am Dent Assoc 1980;101:603-608.

5. Flynn AA. Oral Health Products in Handbook of Nonprescription Drugs. Washington, DC, American Pharmaceutical Association. 1996.