英文药名：ECOZA(Econazole Nitrate)Topical Foam,1%

中文药名：硝酸益康唑泡沫

生产厂家：Quinnova制药
药品介绍
2014年3月18日，美国食品药品监督管理局批准ECOZA（硝酸益康唑）的局部泡沫，1％。 ECOZA泡沫被指示为叉指癣的治疗足癣由红色毛癣菌，须毛癣菌，和在患者12岁及以上的絮状表皮癣菌引起。
ECOZA泡沫，为趾间足癣（趾间脚气）的治疗的新选择，结合Proderm技术®的皮肤恢复性硝酸益康唑的抗真菌证明疗效。事实证明，杀的时候，连续4周施一次，每天造成趾间足癣真菌，其独特的，无酒精泡沫输送帮助保护和恢复肌肤，迅速渗透，不油腻的残留物，它是其他面霜和凝胶之间的共同快速干燥。
ECOZA泡沫，第一个也是唯一美国FDA批准的处方硝酸益康唑泡沫。硝酸益康唑是一种安全有效的外用抗真菌药的专利Proderm技术®，由促进药物成分的渗入真皮层的独特的化学结构，安全有效的替代传统的面霜和凝胶”。
关于ECOZA（硝酸益康唑）的局部泡沫，1％。
ECOZA泡沫是一种处方药，在皮肤上（局部），用于治疗脚气是人们在12岁及以上脚趾（趾间脚气）之间。 ECOZA泡沫应适用于每日一次，连续4周覆盖受影响的区域。 ECOZA泡沫仅用于局部使用和不用于口服，眼，或阴道内的使用。
二双盲，平行组，车辆对照，多中心临床试验中，495科目12岁的临床诊断趾间足癣真菌培养阳性在基线皮肤癣菌收到ECOZA泡沫（N = 246）或泡沫车辆（N = 249）。受试者施加ECOZA泡沫或泡沫车辆每天一次，连续4周。主要终点是谁取得完全治愈（负氢氧化钾，负真菌培养，没有通过的所有症状和体征完全消退指示临床疾病的证据）2周治疗后（43日）的比例。次要终点包括真菌学治愈（KOH消极和负面的文化）和有效的治疗方法（真菌学治愈+无或轻度红斑和/或缩放和所有其他症状和体征不存在）。
从临床研究结果表明，ECOZA泡沫表现出了泡沫车优势的主要和次要终点并表现出对所有具有高真菌学治愈率评估的病原体有效的抗真菌活性。在第43天（2周后处理）的完全治愈率是ECOZA FOAM组（24.3％），比泡沫车组（3.6％）更高。此外，用硝酸益康泡沫观察真菌学治愈率（67.6％对16.9％），和有效的治疗（48.6％比10.8％）的高率1％比泡沫车辆。
ECOZA泡沫是安全和有安全信息与泡沫车辆可比耐受性良好。期间与ECOZA泡沫的临床试验中最常见的不良反应为应用部位反应，从而发生在两个ECOZA泡沫和车辆臂受试者小于1％。

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ECOZA safely and effectively. See full prescribing information for ECOZA.
ECOZA (econazole nitrate topical foam, 1%) for TOPICAL use
Initial U.S. Approval: 1982
INDICATIONS AND USAGE
Ecoza is an azole antifungal indicated for the treatment of interdigital tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients12 years of age and older. (1)
DOSAGE AND ADMINISTRATION
 For topical use only; not for oral, ophthalmic, or intravaginal use. (2)
Apply once daily for 4 weeks. (2)
DOSAGE FORMS AND STRENGTHS
Foam, 1%. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Contents are flammable. Instruct the patient to avoid heat, flame, and/or smoking during and immediately following application. (5.1)
ADVERSE REACTIONS
During clinical trials with Ecoza topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Ecoza and vehicle arms. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Quinnova Pharmaceuticals at 1-877-660-6263 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 10/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Ecoza (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.
2 DOSAGE AND ADMINISTRATION
Ecoza topical foam, 1% is for topical use only. Ecoza topical foam, 1% is not for oral, ophthalmic, or intravaginal use.
Ecoza topical foam, 1% should be applied to cover affected areas once daily for 4 weeks.
3 DOSAGE FORMS AND STRENGTHS
Foam, 1%. Each gram of Ecoza topical foam, 1%, contains 10 mg of econazole nitrate in a white to off-white foam.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Flammability
Ecoza 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.
6 ADVERSE REACTIONS
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 Ecoza topical foam or vehicle (246 subjects were exposed to Ecoza 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 Ecoza topical foam, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the Ecoza and vehicle arms.  
7 DRUG 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.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled trials with Ecoza topical foam in pregnant women. Ecoza topical foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
8.3 Nursing Mothers
It is not known whether econazole nitrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when econazole nitrate is administered to a nursing woman. Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups.
8.4 Pediatric Use
Of the 173 subjects treated with Ecoza topical foam, 1% in the clinical trials, 2 subjects were 12 to 17 years old.  In a pediatric maximal use trial, Ecoza topical foam, 1% was applied once daily to eighteen subjects aged 12 to 17 years with interdigital tinea pedis for 28 days [see Clinical Pharmacology (12.3)]. The safety findings for subjects 12 to 17 years were similar to those in adult population.
8.5 Geriatric Use
Of the 173 subjects treated with Ecoza topical foam, 1% in the adult clinical trials, 6 subjects were 65 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
11 DESCRIPTION
Ecoza (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 Ecoza topical foam, 1% contains 10 mg of econazole nitrate, USP, in a white to off-white foam. Ecoza 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 C18H15Cl3N2O.HNO3 and a molecular weight of 444.70. Its molecular structure is as follows:

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ecoza topical foam is an azole antifungal [see Clinical Pharmacology (12.4)].
12.2 Pharmacodynamics
The pharmacodynamics of Ecoza topical foam, 1% have not been established.
12.3 Pharmacokinetics
The systemic absorption of Ecoza topical foam, 1% following topical application was studied in one clinical trial in adults and one clinical study in pediatric subjects.
In the adult trial, 19 subjects (male and female) with tinea pedis applied Ecoza topical foam, 1% once daily for 29 days.  Subjects applied a mean daily amount of 2.4 g of Ecoza topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles. Blood samples were obtained on Day 29 at pre-dose and 1, 2, 4, 6, 8, and 12 hours after application.  Results (mean ± SD) showed the time to reach peak plasma concentrations (Tmax) was 6.8 ± 5.1 h with maximum concentration (Cmax) of 417 ± 218 pg/ml. The area under the concentration time curve for the first 12 hours post application on Day 29 (AUC(0-12)) was 3440 ± 1920 pg-h/ml. 
In the pediatric trial, 18 subjects (male and female ages 12 to 17) with interdigital tinea pedis and positive fungal cultures were treated with Ecoza topical foam, 1% once daily for 4 weeks.  Subjects applied a mean daily amount of 3.2 g of Ecoza topical foam, 1% to soles, toes, interdigital spaces and tops of both feet up to the ankles.  Blood samples were obtained on Day 28 at pre-dose and 7 h and 11 h post-dose. The mean ± SD econazole plasma concentration was 397 ± 289, 534 ± 745 and 575 ± 638 pg/mL at pre-dose and 7 h and 11 h post-dose, respectively.  
12.4 Microbiology
Mechanism of Action
Econazole nitrate, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the fungistatic activity of econazole. Mammalian cell demethylation is less sensitive to econazole inhibition.
Activity in vitro and in clinical infections
Econazole nitrate has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].
Trichophyton rubrum
Epidermophyton floccosum
Trichophyton mentagrophytes
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility
Long-term animal studies to determine the carcinogenic potential of Ecoza topical foam have not been performed.
Oral administration of econazole nitrate in rats has been reported to produce prolonged gestation. 
14 CLINICAL STUDIES
In two multi-center, randomized, double-blind, vehicle-controlled clinical trials a total of 505 subjects with interdigital tinea pedis were randomized 1:1 to Ecoza topical foam or vehicle; subjects applied the assigned medication once daily for 4 weeks. The severity of erythema, scaling, fissuring, maceration, vesiculation, and pruritus were graded using a 4-point scale (none, mild, moderate, severe). Subjects had KOH examination and fungal cultures taken to confirm eligibility. A total of 339 subjects with positive fungal cultures were evaluated for efficacy. Efficacy was evaluated on Day 43, 2 weeks post-treatment with treatment success being defined as complete cure (negative KOH and fungal culture and no evidence of clinical disease). The study population ranged in age from 12 to 71 years with 5 subjects less than 18 years of age at baseline. The subjects were 71% male and 51% Caucasian. Table 1 presents the efficacy results for each trial.
Table 1: Efficacy Results at Two Weeks Post-treatment (Day 43) Complete Cure, Effective Treatment and Mycological Cure

Trial 1		Trial 2
	Ecoza topical foam,  1%  N=82  n(%)	Foam Vehicle  N=83  n(%)	Ecoza topical foam,  1%  N=91  n(%)	Foam Vehicle  N=83  n(%)
Complete curea	19 (23.2%)	2 (2.4%)	23 (25.3%)	4 (4.8%)
Effective treatmentb	40 (48.8%)	9 (10.8%)	44 (48.4%)	9 (10.8%)
Mycological curec	56 (68.3%)	13 (15.7%)	61 (67.0%)	15 (18.1%)
aMycological cure and an absence of clinical signs and symptoms (erythema, scaling, fissuring, maceration, vesiculation, or pruritus).
bMycological cure and no or mild erythema and/or scaling with all other signs and symptoms absent.
cNegative KOH and Fungal culture.

16 HOW SUPPLIED/STORAGE AND HANDLING
Ecoza topical foam, 1% is white to off-white foam supplied in 70 g (NDC 23710-100-70) aluminum pressurized canister.
Store at controlled room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Do not refrigerate or freeze.
Ecoza 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.
17 PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information)
The patient should be instructed as follows:
Inform patients that Ecoza (econazole nitrate) topical foam, 1% is for topical use only. Ecoza (econazole nitrate) topical foam, 1% is not intended for oral, intravaginal, or ophthalmic use.
Ecoza topical foam, 1% is flammable; avoid heat, flame, and smoking during and immediately following application.
If a reaction suggesting sensitivity or chemical irritation develops with the use of Ecoza topical foam, 1%, use of the medication should be discontinued.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=998798bc-5c64-4e4c-a0d6-925278ff76a4