Amlexenox

Amlexanox appears to have antiallergic and anti-inflammatory effects.

As a benzopyran-bipyridine carboxylic acid derivative, amlexanox has anti-inflammatory and antiallergic properties. It inhibits the chemical mediator release of the slow-reacting substance of anaphylaxis (SRS-A) and is said to have antagonistic effects on interleukin-3. When cells experience stress, they are said to release an inactive form of human fibroblast growth factor 1 (FGF-1), which is a potent mitogen (the entity that causes mitosis). Amlexanox binds to FGF1, while increasing its conformational stability, and sterically blocking Cu(2+) induced oxidation which generally leads to the activation of FGF-1.

Amlexanox had been approved for the treatment as well as relieving the symptoms and maintenance of episodes of Aphthous ulcers.

Most of the drug gets absorbed through a part of the active ulcer. The half-life for the elimination of Amlexenox was found to be 3.5 +/- 1.1 hours in healthy individuals. About 17% of the dose of Amlexenox is found to be eliminated into the urine in the unchanged form of amlexanox, which is a hydroxylated metabolite, as well as their conjugates.

The common side effects associated with Amlexenox are a stinging and burning sensation on the area of application, slight pain, nausea, diarrhea, etc.

Amlexanox is available in the form of oral mucous paste. Amlexenox is available in the UK, Austria, Germany, Greece, Finland, Ireland, Luxembourg, the Netherlands, Norway, Portugal, and Sweden.

Amlexanox appears to have antiallergic and anti-inflammatory effects.

As a benzopyran-bipyridine carboxylic acid derivative, amlexanox has anti-inflammatory and antiallergic properties. It inhibits the chemical mediator release of the slow-reacting substance of anaphylaxis (SRS-A) and is said to have antagonistic effects on interleukin-3. When cells experience stress, they are said to release an inactive form of human fibroblast growth factor 1 (FGF-1), which is a potent mitogen (the entity that causes mitosis). Amlexanox binds to FGF1, while increasing its conformational stability, and sterically blocking Cu(2+) induced oxidation which generally leads to the activation of FGF-1.

Amlexanox has been approved for relieving symptoms and also for the maintenance and treatment of episodes of Aphthous ulcers.

Following a single oral application of 100 mg of paste of Amlexenox, the maximal serum levels were found to be approximately 120 ng/ml are observed at 2.4 hours.

Amlexanox can be used in the treatment of:

• Aphthous ulcers

Amlexanox is approved for use in the following clinical indications:

• Aphthous ulcers

1. The paste should be applied after noticing the symptoms of an aphthous ulcer.
2. The paste should be continued to be used four times daily, preferably after oral hygiene after breakfast, lunch, dinner, or at bedtime.
3. The ulcer should be dried by gently patting it with a soft, clean cloth.
4. The hands should be washed before applying the Amlexanox.
5. The tip of the index finger should be moistened.
6. The paste should be squeezed approximately 1/4 inch (0.5 cm) onto a fingertip.
7. The paste should be dabbed onto the ulcer.
8. Hands should be washed immediately, and paste should be kept out of the reach of children.

Oral paste: 5% Amlexanox

Oral paste

Maintaining health and cessation of smoking are a must.

Caffeine should be limited to use or avoided as it might lead to the risk of nervousness, rapid heartbeat, nausea, palpitations, etc.

Patients with an underlying liver disorder or liver dysfunction must avoid drinking alcohol.

A diet containing food with high sugar content and carbohydrates should be restricted. This includes pies, cakes, honey, cookies, jams, candies, chips, and bread. It is also advised to reduce or limit the intake of cholesterol and saturated fat and instead choose poultry, lean meat, or fish.

The dietary restrictions need to be individualized as per the patient's requirements.

Amlexanox may be contraindicated under the following conditions:

• Hypersensitivity to the ingredients of the medication

There has been found to be no sufficient scientific information regarding warnings and precautions related to the Amlexanox.

Avoid alcohol usage while on Amlexanox medication as alcohol can worsen the effects of any other underlying disease condition, including conditions such as blurred vision, dizziness, etc.

Amlexanox was reported to be found in the milk of lactating rats; therefore, it is advised that caution should be exercised when administering amlexanox oral paste, 5%, to a nursing woman.

Pregnancy Category B: Teratology clinical studies were performed with rabbits and rats at doses up to 206 times, respectively, the projected human daily dose, on an mg/m2 basis. No adverse fetal effects had been observed. At doses up to 200 times the projected human daily dose, on an mg/m2 basis, amlexanox did not have a significant effect on the pre- and postnatal development of rat fetuses. There are found to be no adequate as well as well-controlled studies in pregnant women. As reproduction studies are not always predictive of the responses of the humans, amlexanox should be used during pregnancy only if the it is clearly needed.

There has been found to be no sufficient scientific evidence traceable regarding the safety and use of Amlexanox in concurrent use with any particular food.

The adverse reactions related to Amlexanox can be categorized as:

Rare

• Increased mouth sores
• Swelling of your tongue, face, lips, or throat
• Hives
• Difficulty breathing
• Severe dizziness
• Nausea
• Diarrhea

The common side effects of Amlexenox include the following:

Pregnancy

Pregnancy Category B: Teratology clinical studies were performed with rabbits and rats at doses up to 206 times, respectively, the projected human daily dose, on an mg/m2 basis. No adverse fetal effects had been observed. At doses up to 200 times the projected human daily dose, on an mg/m2 basis, amlexanox did not have a significant effect on the pre- and postnatal development of rat fetuses. There are found to be no adequate as well-controlled studies in pregnant women. As reproduction studies are not always predictive of the responses of the humans, amlexanox should be used during pregnancy only if it is clearly needed.

Nursing Mothers

Amlexanox was reported to be found in the milk of lactating rats; therefore, it is advised that caution should be exercised when administering amlexanox oral paste, 5%, to the nursing woman.

Pediatric Use

Effectiveness and safety of amlexanox oral paste, 5%, in pediatric patients is not established.

Geriatric Use

Clinical studies of Amlexanox did not include sufficient numbers of subjects who were aged 65 and over to determine whether they respond any differently from the younger subjects. Other reported clinical experience had not identified differences in responses between the older and younger patients. In general, dose selection for an older patient should be done cautiously, usually starting at the low dosing range, reflecting the greater frequency of decreased renal, hepatic, or cardiac function, and of concomitant disease or any other drug therapy

There are no reports of human ingestion overdose. The ingestion of a full tube of 5 grams of paste has resulted in systemic exposure well below the maximum the nontoxic dose of amlexanox in animal studies. Gastrointestinal problems such as diarrhea and vomiting could occur as a result from an overdose.

Pharmacodynamics

Amlexanox is said to be a mucoadhesive oral paste which has been clinically proven to prevent the onset, accelerate healing and resolve the pain associated with aphthous ulcers or the canker sores. It is said to decrease the time ulcers take to heal. As amlexanox decreases the healing time, it is also said to decrease the pain one feels. Recent studies have also shown that the majority of ulcers can be prevented by the application of the paste during the prodromal i.e.pre-ulcerative phase of the disease. Recurrent Aphthous Ulcers (RAU) which is also known as Recurrent Aphthous Stomatitis (RAS) is recognized to be the most common oral mucosal disease known to man. The estimates suggest that 20% - 25% of the general population suffer at least one incidence of aphthous ulcers every year. Amlexanox is also found to being investigated for its anti-allergenic and anti-inflammatory properties.

Pharmacokinetics

Following a single oral application of 100 mg of paste i.e. 5 mg amlexanox, a maximal serum level of approximately 120 ng/ml had been observed at 2.4 hours. Most of the systemic absorption of amlexanox occurs via the gastrointestinal tract, and the amount of Amlexanox absorbed directly through the active ulcer is not as significant as the applied dose. The half-life for elimination was found to be 3.5 +/- 1.1 hours in healthy individuals. Approximately 17% of the dose of Amlexanox is eliminated into the urine in an unchanged form of amlexanox, which is a hydroxylated metabolite, and their conjugates. After multiple applications 4 times daily, steady state levels were found to be reached within 1 week, and no accumulation had been observed with up to four weeks of usage.

• Yi Dong, Jie Liu, Zhi Wang, Xiaobo Zhong et.al.A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial.

1. https://docs.google.com/document/d/1jjgyJStm76E5WcTFR9O5vvuAULbaFrNe/edit
2. https://www.drugs.com/history/oradisc-a.html
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20511s002lbl.pdf
4. https://www.rxlist.com/aphthasol-side-effects-drug-center.htm
5. https://medlineplus.gov/druginfo/meds/a601017.html
6. https://www.rxwiki.com/amlexanox
7. https://pubchem.ncbi.nlm.nih.gov/compound/Amlexanox#section=ATC-Code