ECONAZOLE: 450 Adverse Event Reports & Safety Profile

Econazole nitrate topical foam, 1% contains the azole antifungal agent, econazole nitrate in an oil-in-water emulsion base consisting of the following inactive ingredients: dimethicone, glycerin, polysorbate 20, povidone, propylene glycol, stearic acid, trolamine, purified water and butane as a propellant. Each gram of econazole nitrate topical foam, 1% contains 10 mg of econazole nitrate, USP, in a white to off-white foam. Econazola nitrate topical foam, 1% is alcohol (ethanol)-free and for topical use only. Chemically, econazole nitrate is 1-[2-{(4-chloro-phenyl)methoxy}-2-(2,4-dichlorophenyl) ethyl]-1H-imidazole mononitrate. Econazole nitrate has the molecular formula C 18 H 15 Cl 3 N 2 O. HNO 3 and a molecular weight of 444.70. Its molecular structure is as follows: Chemical Structure

AND USAGE Econazole nitrate topical foam, 1%, is indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 12 years of age and older. Econazole nitrate is an azole antifungal indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes , and Epidermophyton floccosum in patients 12 years of age and older. ( 1 )

DOSAGE AND ADMINISTRATION Sufficient econazole nitrate cream, 1%, should be applied to cover affected areas once daily in patients with tinea pedis, tinea cruris, tinea corporis, and tinea versicolor, and twice daily (morning and evening) in patients with cutaneous candidiasis. Early relief of symptoms is experienced by the majority of patients and clinical improvement may be seen fairly soon after treatment is begun; however, candidal infections and tinea cruris and corporis should be treated for two weeks and tinea pedis for one month in order to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be redetermined. Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.

CONTRAINDICATIONS Econazole Nitrate Cream is contraindicated in individuals who have shown hypersensitivity to any of its ingredients.

REACTIONS - During clinical trials with econazole nitrate topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the econazole nitrate and vehicle arms. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Trifluent Pharma at 1-800-927-5191 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See

17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 09/2025

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two double-blind, vehicle-controlled clinical trials, 495 subjects were exposed to econazole nitrate topical foam or vehicle (246 subjects were exposed to econazole nitrate topical foam, 1% and 249 were exposed to vehicle). Subjects with interdigital tinea pedis applied foam or vehicle once daily for approximately 28 days. During clinical trials with econazole nitrate topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the econazole nitrate and vehicle arms.

AND PRECAUTIONS - Contents are flammable. Instruct the patient to avoid heat, flame, and/or smoking during and immediately following application. ( 5.1 )

5.1 Flammability Econazole nitrate topical foam is flammable. Avoid heat, flame, and smoking during and immediately following application. Contents under pressure. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C) even when empty. Do not store in direct sunlight.

PRECAUTIONS General If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued. For external use only. Avoid introduction of Econazole Nitrate Cream into the eyes.

Drug Interactions Warfarin

Concomitant administration of econazole and warfarin has resulted in enhancement of anticoagulation effect. Most cases reported product application with use under occlusion, genital application, or application to large body surface area which may increase the systemic absorption of econazole nitrate. Monitoring of International Normalized Ratio (INR) and/or prothrombin time may be indicated especially for patients who apply econazole to large body surface areas, in the genital area, or under occlusion. Carcinogenesis, mutagenesis, impairment of fertility Long-term animal studies to determine carcinogenic potential have not been performed. Oral administration of econazole nitrate in rats has been reported to produce prolonged gestation. Intravaginal administration in humans has not shown prolonged gestation or other adverse reproductive effects attributable to econazole nitrate therapy.

Pregnancy

Econazole nitrate has not been shown to be teratogenic when administered orally to mice, rabbits or rats. Fetotoxic or embryotoxic effects were observed in Segment I oral studies with rats receiving 10 to 40 times the human dermal dose. Similar effects were observed in Segment II or Segment III studies with mice, rabbits and/or rats receiving oral doses 80 or 40 times the human dermal dose. Econazole nitrate should be used in the first trimester of pregnancy only when the physician considers it essential to the welfare of the patient. The drug should be used during the second and third trimesters of pregnancy only if clearly needed.

Nursing

Mothers It is not known whether econazole nitrate is excreted in human milk. Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups. Also, in lactating rats receiving large oral doses (40 or 80 times the human dermal dose), there was a reduction in post partum viability of pups and survival to weaning; however, at these high doses, maternal toxicity was present and may have been a contributing factor. Caution should be exercised when econazole nitrate is administered to a nursing woman.

Geriatric Use

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

INTERACTIONS -

7.1 Warfarin Concomitant administration of econazole and warfarin has resulted in enhancement of anticoagulant effect. Most cases reported product application with use under occlusion, genital application, or application to a large body surface area which may increase the systemic absorption of econazole nitrate. Monitoring of International Normalized Ratio (INR) and/or prothrombin time may be indicated especially for patients who apply econazole to large body surface areas, in the genital area, or under occlusion.