Amlexanox

Adverse reactions considered related or possibly related to amlexanox oral paste, 5%, were not reported by more than 5% of patients. Adverse reactions reported by 1-2% of patients were transient pain, stinging and/or burning at the site of application. Infrequent ( < 1%) adverse reactions in the clinical studies were contact mucositis, nausea, and diarrhea.

There are no reports of human ingestion overdosage. Ingestion of a full tube of 5 grams of paste would result in systemic exposure well below the maximum nontoxic dose of amlexanox in animals. Gastrointestinal upset such as diarrhea and vomiting could result from an overdose.

The mechanism of action by which amlexanox accelerates healing of aphthous ulcers is unknown. In vitro studies have demonstrated amlexanox to be a potent inhibitor of the formation and/or release of inflammatory mediators (histamine and leukotrienes) from mast cells, neutrophils and mononuclear cells. Given orally to animals, amlexanox has demonstrated anti-allergic and anti-inflammatory activities and has been shown to suppress both immediate and delayed type hypersensitivity reactions. The relevance of these activities of amlexanox to its effects on aphthous ulcers has not been established.

Pharmacokinetics and Metabolism

After a single oral application of 100 mg of paste (5 mg amlexanox), maximal serum levels of approximately 120 ng/ml are observed at 2.4 hours. Most of the systemic absorption of amlexanox is via the gastrointestinal tract, and the amount absorbed directly through the active ulcer is not a significant portion of the applied dose. The half-life for elimination was 3.5 +/- 1.1 hours in healthy individuals. Approximately 17% of the dose is eliminated into the urine as unchanged amlexanox, a hydroxylated metabolite, and their conjugates. With multiple applications four times daily, steady state levels were reached within one week, and no accumulation was observed with up to four weeks of usage.

Clinical Studies

The safety of amlexanox oral paste, 5%, was established in a study in which 100 patients with aphthous ulcers applied the medication four times daily for 28 days with no significant topical or systemic adverse effects. The effectiveness was demonstrated in three controlled clinical studies of patients with mild to moderate aphthous ulcers which evaluated 464 patients receiving amlexanox oral paste, 5%, 465 patients receiving a placebo paste, and 195 patients receiving no treatment. Amlexanox oral paste, 5%, was shown to accelerate healing of aphthous ulcers in a statistically significant manner as compared to both vehicle and no treatment.

In the combined database of the two studies including a no treatment group, there was a significant difference in the rate of ulcer healing which translated to a reduction of 1.6 days in the median time to complete healing and a reduction of 1.3 days in the median time to complete pain relief. After 3 days of treatment there was a significant difference in both percent of patients with complete healing of ulcers (21% vs. 8%) and percent of patients with complete resolution of pain (44% vs. 20%).

In the combined database of the three studies, there was a significant difference in the rate of ulcer healing which translated into a reduction of 0.7 days in the median time to complete healing, and a reduction of 0.7 days in the median time to complete pain relief. After 4 days of treatment there was a significant difference in both percent of patients with complete healing of ulcers (37% vs. 27%) and percent of patients with complete resolution of pain (60% vs. 49%).

Pain relief occurred in conjunction with healing of the ulcers. Amlexanox oral paste, 5%, by itself, was not shown to be an analgesic medication. The safety and effectiveness of the product in immunocompromised individuals has not been assessed.

Cumulative % of Patients with Healed Ulcers

Results for amlexanox, 5%, vs. vehicle are based on three clinical trials. Results for amlexanox, 5%, vs. no treatment are based on two clinical trials.
* denotes statistically significant superiority of amlexanox, 5%, vs. vehicle and no treatment.
# denotes statistically significant superiority of amlexanox, 5%, vs. no treatment.
Error bars represent Standard Error of the Mean.

Contraindications

Hypersensitivity

Cautions

Re-evaluate if not healed in 10 days

Discontinue if rash or contact mucositis develops

Pregnancy Category: B

Lactation: excretion in milk unknown; use with caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Amlexanox is available in the following forms:

• Oral Paste

Aphthous ulcer healing agent.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Applies to amlexanox topical: paste

Along with its needed effects, amlexanox topical may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Some side effects of amlexanox topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning, stinging, or pain at place medicine is applied
• inflammation of mucous membranes
• diarrhea
• nausea

There are no data on the excretion of amlexanox into human milk. It has been found in the milk of lactating rats. The manufacturer recommends that caution be used when administering amlexanox to nursing women.