Amlexanox

Amlexanox is a benzopyrano-pyridine carboxylic acid with anti-allergic and anti-inflammatory activity. In the US, its only FDA-approved product was Aphthasol (amlexanox oral paste 5%), which is no longer marketed. Oral amlexanox tablets are marketed outside the US for bronchial asthma and allergic rhinitis. Lake Hills Pharmacy uses amlexanox bulk drug substance in compounded oral capsules.

Aphthasol was labeled for the treatment of the signs and symptoms of aphthous ulcers in people with normal immune systems. No US labeling exists for oral systemic use, and all oral capsule use is off-label.

Prescribers use compounded oral amlexanox for allergic and mast cell–related conditions and for metabolic conditions such as obesity-associated insulin resistance and type 2 diabetes, which have been studied in small clinical trials.

Amlexanox inhibits the release of histamine and leukotrienes from mast cells and other inflammatory cells. It also inhibits the non-canonical IkappaB kinases TBK1 and IKK-epsilon. These kinases are upregulated in adipose tissue and liver in obesity and are implicated in obesity-associated inflammation and reduced energy expenditure, which is the rationale for its metabolic use.

Aphthasol labeling notes that most of a dose applied to oral ulcers is swallowed and absorbed from the gastrointestinal tract. Peak plasma concentrations occur roughly 2 hours after dosing and the elimination half-life is about 3.5 hours. Amlexanox is excreted mainly in the urine as unchanged drug and as hydroxylated and conjugated metabolites. Pharmacokinetics of higher oral systemic doses are less well described in US sources.

• Hypersensitivity to amlexanox or any component of the formulation.

• Systemic safety data in US labeling are limited because the only US product was a topical oral paste.
• Stop the drug if rash, urticaria or other hypersensitivity reactions occur.
• Use caution in hepatic or renal impairment, which may reduce clearance.

No clinically significant drug interactions are established. Review the full medication list, including other anti-inflammatory and antidiabetic therapies, before starting.

Oral paste: transient pain, stinging or burning at the application site, and rarely contact mucositis. Oral systemic use: nausea, diarrhea, abdominal discomfort, headache and rash have been reported; hypersensitivity reactions are uncommon.

Animal reproduction studies described in Aphthasol labeling did not show fetal harm, but adequate human data are lacking. Whether amlexanox is excreted in human milk is unknown. Use only if the prescriber judges the benefit to justify the risk.

Clinical response and tolerability, signs of hypersensitivity, and laboratory measures appropriate to the condition being treated, such as glucose or hemoglobin A1c in metabolic use. Consider liver and renal function in patients with impairment or on long-term therapy.

• Aphthasol (amlexanox oral paste) 5% Prescribing Information, Block Drug Company.
• Martindale: The Complete Drug Reference, amlexanox monograph.