Econazole

Econazole is an antifungal agent belonging to the pharmacological class of Imidazole.

Econazole has been approved to relieve symptoms and also for the treatment and maintenance of Cutaneous Candidiasis, Tinea Infections, Tinea corporis, Tinea cruris, Tinea versicolor.

Econazole is absorbed intravaginally with absorption ranging from 30%to 40% of an intravaginal application.

The common side effects involved in using Econazole are Hives, Difficulty breathing, Itching, Swelling of the face, lips, tongue, or throat, Severe dizziness, Rash.

Econazole is available in the form of Topical cream , Topical Foam.

Econazole is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Econazole belonging to the pharmacological class of Imidazole acts as an antifungal agent.

Econazole functions by interacting with 14-α demethylase, a cytochrome P-450 enzyme crucial for converting lanosterol into ergosterol. Ergosterol is a vital element in the fungal cell membrane, and when its synthesis is inhibited, it leads to enhanced cellular permeability, causing the leakage of cellular contents. Apart from that, Econazole may also hinder endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts into mycelial forms, impede purine uptake, and disrupt the biosynthesis of triglycerides and/or phospholipids.

Econazole has been approved to relieve symptoms and also for the treatment and maintenance of Cutaneous Candidiasis, Tinea Infections, Tinea corporis, Tinea cruris, Tinea versicolor.

In a trial for adults, both male and female subjects with tinea pedis were given Econazole Nitrate Foam, 1% to apply once daily for 29 days. On average, subjects applied 2.4 g of the foam to the soles, toes, interdigital spaces, and tops of both feet up to the ankles. Blood samples were taken on Day 29 before and 1, 2, 4, 6, 8, and 12 hours after applying the foam. The results (mean ± SD) showed that the maximum concentration (Cmax) of Econazole in plasma was 417 ± 218 pg/ml. It took 6.8 ± 5.1 hours for the plasma concentration to reach its peak (Tmax) after applying Econazole Nitrate Foam.

Econazole is found to be available in the form of Topical cream , Topical Foam.

Econazole can be used in the following treatment:

• Cutaneous Candidiasis
• Tinea Infections
• Tinea corporis
• Tinea cruris
• Tinea versicolor

Econazole can help to relieve symptoms and also for the treatment and maintenance of Cutaneous Candidiasis, Tinea Infections, Tinea corporis, Tinea cruris, Tinea versicolor.

Econazole is approved for use in the following clinical indications:

• Cutaneous Candidiasis
• Tinea Infections
• Tinea corporis
• Tinea cruris
• Tinea versicolor

• Cutaneous Candidiasis:

For Cutaneous candidiasis, use a topical cream containing 1%. Apply an adequate amount of the cream twice daily, in the morning and evening, for a duration of 2 weeks.

• Tinea Infections:

Tinea corporis/tinea cruris: Apply a topical cream with 1% concentration to the affected and surrounding area(s) once daily until the symptoms subside, which usually takes 1 to 3 weeks.

Tinea pedis (labeled use)/tinea manuum (off-label use): Use a topical cream or foam with 1% concentration on the affected and surrounding area(s) once daily until 1 week after the symptoms have disappeared, generally for a total of 4 weeks .

Tiinea versicolor: For Tinea versicolor, apply a topical cream containing 1% concentration to the affected area(s) and the immediate surrounding skin once daily for a period of 2 weeks .

• Topical Cream: The cream has a 1% concentration.
• Topical Foam (Ecoza): The foam formulation also contains 1% concentration.

Topical cream , Topical Foam.

Dosage Adjustments in Pediatric Patients:

• Cutaneous Candidiasis (including diaper dermatitis):

For infants, children, and adolescents with Cutaneous candidiasis, including diaper dermatitis, there is limited data available. Use a topical cream and apply a sufficient amount to cover the affected area twice daily .

• Tinea corporis, tinea cruris, and tinea versicolor (smaller lesions):

For children and adolescents with Tinea corporis, tinea cruris, and tinea versicolor involving smaller lesions, limited data is available. Apply a topical cream once daily, covering the affected area, for a duration of 4 weeks .

• Tinea pedis:

For children and adolescents with Tinea pedis, there is limited data available. Use a topical cream and apply a sufficient amount to cover the affected area once daily for 4 weeks .

Alternatively, for children aged 12 years and above and adolescents with Tinea pedis, a foam formulation can be used. Apply a sufficient amount to cover the affected area once daily for 4 weeks.

Econazole may be contraindicated under the following conditions:

• Hypersensitivity to econazole nitrate or any of the cream or ovule's components.
• It should not be applied in or around the eyes.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• WARNINGS:

Econazole Nitrate Cream is not intended for use in the eyes (ophthalmic use).

• PRECAUTIONS:

General:

• If a reaction suggesting sensitivity or chemical irritation occurs, discontinue the use of the medication.
• For external use only. Avoid contact with the eyes.

Carcinogenicity Studies:

• Long-term animal studies to determine the potential carcinogenicity of econazole nitrate have not been conducted.

Fertility (Reproduction):

• Oral administration of econazole nitrate in rats has been reported to result in prolonged gestation. However, intravaginal administration in humans has not shown prolonged gestation or other adverse reproductive effects attributed to econazole nitrate therapy.

The excretion of econazole nitrate in human milk is currently unknown. In studies involving lactating rats, administration of econazole nitrate orally resulted in the presence of econazole and/or its metabolites in the milk, which were then found in nursing pups. Furthermore, when lactating rats received large oral doses (40 or 80 times the human dermal dose), there was a decrease in the viability of postpartum pups and their survival to weaning. However, it's important to note that at these high doses, maternal toxicity was also observed, which might have contributed to these effects. Due to these findings, caution is advised when administering econazole nitrate to nursing women.

Pregnancy:

Pregnancy Category C

Oral administration of econazole nitrate to mice, rabbits, and rats did not demonstrate any teratogenic effects. However, fetotoxic or embryotoxic effects were observed in Segment I oral studies conducted on rats, where doses ranging from 10 to 40 times the human dermal dose were used. Similar effects were also observed in Segment II or Segment III studies involving mice, rabbits, and/or rats, receiving oral doses of 80 or 40 times the human dermal dose.

During pregnancy, econazole nitrate should be used cautiously. In the first trimester, it should only be used when the physician considers it essential to the patient's welfare. In the second and third trimesters, the drug should only be used if absolutely necessary and under close medical supervision.

No specific food restrictions or dietary modifications are required when using Econazole. Econazole can be administered with or without food.

The adverse reactions related to Econazole can be categorized as follows:

Common:

• Hives
• Difficulty breathing
• Itching
• Swelling of the face, lips, tongue, or throat
• Severe dizziness
• Rash

Less common:

• Body aches or pain
• Cough
• Difficulty with breathing
• Ear congestion
• Fever or chills
• Headache
• Loss of voice
• Lower back or side pain
• Nasal congestion
• Painful or difficult urination
• Pale skin
• Runny nose
• Sneezing
• Sore throat
• Troubled breathing with exertion
• Unusual bleeding or bruising
• Unusual tiredness or weakness

Rare:

• Black, tarry stools
• Pale skin
• Shortness of breath
• White spots or ulcers in the mouth

There is no sufficient scientific evidence traceable regarding Drug interactions of Econazole.

The following are the side effects involving Econazole:

• Hives
• Difficulty breathing
• Itching
• Swelling of the face, lips, tongue, or throat
• Severe dizziness
• Rash

The use of the molecule Econazole should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category C

Oral administration of econazole nitrate to mice, rabbits, and rats did not demonstrate any teratogenic effects. However, fetotoxic or embryotoxic effects were observed in Segment I oral studies conducted on rats, where doses ranging from 10 to 40 times the human dermal dose were used. Similar effects were also observed in Segment II or Segment III studies involving mice, rabbits, and/or rats, receiving oral doses of 80 or 40 times the human dermal dose.

During pregnancy, econazole nitrate should be used cautiously. In the first trimester, it should only be used when the physician considers it essential to the patient's welfare. In the second and third trimesters, the drug should only be used if absolutely necessary and under close medical supervision.

Lactation:

The excretion of econazole nitrate in human milk is currently unknown. In studies involving lactating rats, administration of econazole nitrate orally resulted in the presence of econazole and/or its metabolites in the milk, which were then found in nursing pups. Furthermore, when lactating rats received large oral doses (40 or 80 times the human dermal dose), there was a decrease in the viability of postpartum pups and their survival to weaning. However, it's important to note that at these high doses, maternal toxicity was also observed, which might have contributed to these effects. Due to these findings, caution is advised when administering econazole nitrate to nursing women.

Pediatric:

Current research and studies conducted thus far have not revealed any pediatric-specific issues that would restrict the effectiveness of econazole topical foam in children aged 12 years and older. However, it is important to note that the safety and efficacy of the foam have not been established for children below the age of 12 years.

Geriatric Use:

There is no sufficient scientific evidence traceable regarding use and safety of Econazole in Geriartric use.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Econazole.

As of the present date, there have been no reported cases of overdosage of econazole nitrate in humans. However, in animal studies conducted on mice, rats, guinea pigs, and dogs, oral LD50 values were observed at 462 mg/kg, 668 mg/kg, 272 mg/kg, and over 160 mg/kg, respectively.

Pharmacodynamics:

Econazole belongs to a class of antifungal medications that includes fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Its mechanism of action involves inhibiting the production of essential substances necessary for the growth and function of fungal organisms. It is essential to note that econazole is specifically effective against fungal infections and does not have any impact on bacterial or viral infections.

Pharmacokinetics:

● In this study, one gram of econazole-3H nitrate topical cream (equivalent to 10 mg of econazole-3H nitrate) was applied under occlusive dressing to the shaved backs of two groups, each consisting of six female rabbits. The application site of one group was abraded for comparison. The results showed that approximately 35% and 30% of the administered dose was absorbed through the abraded and unabraded skin, respectively. Notably, percutaneous absorption was nearly complete within four days, with peak levels of radioactivity observed in plasma and tissues 24 hours after dosing in both groups. The absorption was primarily through the epidermis of hair follicles.

● Additionally, a cream formulation containing 5 mg of econazole nitrate (ranging from 1.43 to 2.17 mg/kg) was administered intravaginally to rabbits. Findings indicated that 30 to 40% of the drug was absorbed through this route of administration.

● Furthermore, in a separate experiment involving dogs, miniaturized ovules delivering either 0.96 or 2.48 mg/kg of econazole nitrate were individually administered intravaginally. The estimated rates of vaginal absorption were found to be 0.87% and 1.10%, respectively.

● In another part of the study with dogs, intravaginal administration of 1% or 2% cream formulations containing econazole nitrate at doses of 10 mg/dog (1.01-1.28 mg/kg), 1 mg/kg, and 2 mg/kg were conducted. The estimated rates of vaginal absorption were approximately 27%, 12.4 - 15.2%, and 4.9%, respectively, for each dose.

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