Benecut

advertisement
How old is patient?

Benecut uses


1 INDICATIONS AND USAGE

Benecut Cream is indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum.

Benecut Cream is an allylamine antifungal indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum. (1)

2 DOSAGE AND ADMINISTRATION

For topical use only. Benecut Cream is not for ophthalmic, oral, or intravaginal use. Apply a thin layer of Benecut Cream once-daily to the affected areas plus a ½ inch margin of healthy surrounding skin for 2 weeks.

For topical use only. Benecut Cream is not for ophthalmic, oral, or intravaginal use. (2)

Apply a thin layer of Benecut Cream once-daily to the affected areas plus a ½ inch margin of healthy surrounding skin for 2 weeks. (2)

3 DOSAGE FORMS AND STRENGTHS

Each gram of Benecut Cream contains 20 mg of Benecut (2%) in a white to off-white base.

Cream: 2% (3)

4 CONTRAINDICATIONS

None

None (4)

5 WARNINGS AND PRECAUTIONS

Discontinue treatment if redness or irritation develops with Benecut Cream use.

5.1 Local Adverse Reactions

Discontinue treatment if irritation or sensitivity develops with the use of Benecut Cream. Direct patients to contact their physician if these conditions develop following use of Benecut Cream.

advertisement

6 ADVERSE REACTIONS

The most common adverse reaction is pruritus. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 clinical practice.

During clinical trials, 903 subjects were exposed to naftifine 1% and 2% cream formulations. A total of 564 subjects with interdigital tinea pedis, tinea cruris, or tinea corporis were treated with Benecut Cream.

In two randomized, vehicle-controlled trials (400 patients were treated with Benecut Cream). The population was 12 to 88 years old, primarily male (79%), 48% Caucasian, 36% Black or African American, 40% Hispanic or Latino and had either predominantly interdigital tinea pedis or tinea cruris. Most subjects received doses once-daily, topically, for 2 weeks to cover the affected skin areas plus a ½ inch margin of surrounding healthy skin. In the two vehicle-controlled trials, 17.5% of Benecut Cream treated subjects experienced an adverse reaction compared with 19.3% of vehicle subjects. The most common adverse reaction (≥1%) is pruritus. Most adverse reactions were mild in severity. The incidence of adverse reactions in the Benecut Cream treated population was not significantly different than in the vehicle treated population.

In a third randomized, vehicle-controlled trial, 116 pediatric subjects with tinea corporis were treated with Benecut Cream. The population was aged ≥2 to <18 years (mean age of 9 years), predominately male (61%), 47% White, 51% Black or African American, 92% Hispanic or Latino, and infected with tinea corporis. Benecut Cream was topically applied once daily for 2 weeks to all affected body surface areas with tinea corporis plus a ½ inch margin of healthy skin surrounding the affected lesions. The incidence of adverse reactions in the Benecut Cream treated population was not significantly different than in the vehicle treated population.

In two open-label pediatric pharmacokinetics and safety trials, 49 pediatric subjects 2 to <18 years of age with interdigital tinea pedis, tinea cruris, and tinea corporis received Benecut Cream. The incidence of adverse reactions in the pediatric population was similar to that observed in the adult population.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Benecut: redness/irritation, inflammation, maceration, swelling, burning, blisters, serous drainage, crusting, headache, dizziness, leukopenia, agranulocytosis.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

advertisement

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data with Benecut Cream in pregnant women to inform the drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, no adverse effects on embryofetal development were seen at oral doses administered during the period of organogenesis up to 18 times the maximum recommended human dose in pregnant rats or subcutaneous doses administered during the period of organogenesis up to 2 times the MRHD in pregnant rats or 4 times the MRHD in pregnant rabbits .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Systemic embryofetal development studies were conducted in rats and rabbits. For the comparison of animal to human doses based on body surface area comparison (mg/m2), the MRHD is set at 8 g 2% cream per day (2.67 mg/kg/day for a 60 kg individual).

Oral doses of 30 mg/kg/day, 100 mg/kg/day and 300 mg/kg/day Benecut were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal development were noted at doses up to 300 mg/kg/day (18 times MRHD). Subcutaneous doses of 10 mg/kg/day and 30 mg/kg/day Benecut were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal development were noted at 30 mg/kg/day (2 times MRHD). Subcutaneous doses of 3 mg/kg/day, 10 mg/kg/day and 30 mg/kg/day Benecut were administered during the period of organogenesis to pregnant female rabbits. No treatment related effects on embryofetal development were noted at 30 mg/kg/day (4 times MRHD).

A peri-and post-natal development study was conducted in rats. Oral doses of 30 mg/kg/day, 100 mg/kg/day and 300 mg/kg/day Benecut were administered to female rats from gestational day 14 to lactation day 21. Reduced body weight gain of females during gestation and of the offspring during lactation was noted at 300 mg/kg/day (18 times MRHD). No developmental toxicity was noted at 100 mg/kg/day (6 times MRHD).

8.2 Lactation

Risk Summary

There is no information available on the presence of Benecut Cream in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Benecut Cream to an infant during lactation; therefore, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for Benecut Cream and any potential adverse effects on the breastfed infant from Benecut Cream or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of Benecut Cream have been established in pediatric patients age 12 and above with interdigital tinea pedis and tinea cruris and age 2 and above with tinea corporis .

Use of Benecut Cream in these age groups is supported by evidence from adequate and well controlled studies in adults and children, with additional safety and PK data from two open label trials conducted in 49 pediatric subjects exposed to Benecut Cream .

Safety and effectiveness of Benecut Cream in the treatment of tinea cruris and interdigital tinea pedis in pediatric patients less than 12 years of age have not been established. Safety and effectiveness of Benecut Cream in the treatment of tinea corporis in pediatric patients less than 2 years of age have not been established.

8.5 Geriatric Use

Clinical studies of Benecut Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

advertisement

11 DESCRIPTION

Benecut Cream is a white to off-white cream for topical use only. Each gram of Benecut Cream contains 20 mg of Benecut (2%), a synthetic allylamine antifungal compound.

Chemically, naftifine HCl is (E)-N-Cinnamyl-N-methyl-1-napthalenemethylamine hydrochloride.

The molecular formula is C21H21N∙HCl with a molecular weight of 323.86.

The structural formula of Benecut is:

Benecut Cream contains the following inactive ingredients: benzyl alcohol, cetyl alcohol, cetyl esters wax, hydrochloric acid, isopropyl myristate, polysorbate 60, purified water, sodium hydroxide, sorbitan monostearate, and stearyl alcohol.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Benecut Cream is a topical antifungal drug

12.2 Pharmacodynamics

The pharmacodynamics of Benecut Cream have not been established.

12.3 Pharmacokinetics

In vitro and in vivo bioavailability studies have demonstrated that naftifine penetrates the stratum corneum in sufficient concentration to inhibit the growth of dermatophytes.

The pharmacokinetics of Benecut Cream was evaluated following once-daily topical application for 2 weeks to 21 adult subjects, both males and females, with both tinea pedis and tinea cruris. The median total amount of cream applied was 6.4 g per day. The results showed that the systemic exposure (i.e., maximum concentration (Cmax) and area under the curve from time 0 to 24 hours (AUC0-24)) to naftifine increased over the 2 week treatment period in all the 21 subjects. Geometric mean (coefficient of variation or CV%) AUC0-24 was 117 (41.2) ng*hr/mL on Day 1, and 204 (28.5) ng*hr/mL on Day 14. Geometric mean (CV%) Cmax was 7 ng/mL (55.6) on Day 1 and 11 ng/mL (29.3) on day 14. Median time to Cmax (Tmax) was 8 hours (range: 4 to 24 hours) on Day 1 and 6 hours (range: 0 to 16 hours) on Day 14. Accumulation after 14 days of topical application was less than two fold. Trough concentrations generally increased throughout the 14 day study period. Naftifine continued to be detected in plasma in 13/21 (62%) subjects on day 28, the mean (standard deviation or SD) plasma concentrations were 1.6 ± 0.5 ng/mL (range below limit of quantitation (BLQ) to 3 ng/mL). In the same pharmacokinetic trial conducted in patients with tinea pedis and tinea cruris, median fraction of the dose excreted in urine during the treatment period was 0.0016% on Day 1 versus 0.0020% on Day 14.

In a second trial, that enrolled 22 subjects, the pharmacokinetics of Benecut Cream was evaluated in 20 pediatric subjects 13 to <18 years of age with both tinea pedis and tinea cruris. Subjects were treated with a median dose of 8.1 g (range 6.6 to 10.1 g) applied to the affected areas once daily for 2 weeks. The results showed that the systemic exposure increased over the treatment period. Geometric mean (CV%) AUC0-24 was 138 (50.2) ng*hr/mL on Day 1, and 192 (74.9) ng*hr/mL on Day 14. Geometric mean (CV%) Cmax was 9.21 ng/mL (48.4) on Day 1 and 12.7 ng/mL (67.2) on Day 14. Median fraction of the dose excreted in urine during the treatment period was 0.0030% on Day 1 and 0.0033% on Day 14.

A third trial evaluated the pharmacokinetics of Benecut Cream in 27 pediatric subjects 2 to < 12 years of age with at least moderate tinea corporis. Subjects were divided into younger (ages 2 to < 6 years, 17 subjects) and older (6 to <12 years, 10 subjects) groups. Median doses of 1.3 g (range 1 to 3.1 g) and 2.3 g (range 2.2 to 4.2 g) were applied once-daily for 2 weeks in the younger and older groups, respectively, to the affected area plus a ½ inch margin. Plasma and urine pharmacokinetic assessments were conducted on Day 1 in the older group only and on Day 14 in both groups. All subjects showed measurable levels of naftifine in plasma after topical application of Benecut Cream. Following a single dose on Day 1 in subjects 6 to < 12 years of age, the geometric mean (CV%) values of Cmax and AUC0-24 were 3.60 (76.6) ng/mL and 49.8 (64.4) ng*h/mL, respectively. On Day 14 in this group, the Cmax and AUC0-24 were 3.31 (51.2) ng/mL and 52.4 (49.2) ng*h/mL, respectively. In subjects 2 to < 6 years of age on Day 14, the Cmax and AUC0-24 were 3.98 (186) ng/mL and 54.8 (150) ng*h/mL, respectively. In the older group of subjects 6 to 12 years of age, the systemic exposures (both Cmax and AUC0-24) on Days 1 and 14 were comparable. The median fraction of the dose excreted into urine over 24 hours following drug applications on Day 1 and Day 14 was 0.0029% and 0.0014%, respectively.

12.4 Microbiology

Although the exact mechanism of action against fungi is not known, Benecut appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2, 3-epoxidase. This inhibition of enzyme activity results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells.

Mechanism of Resistance

To date, a mechanism of resistance to naftifine has not been identified.

Naftifine has been shown to be active against most isolates of the following fungi, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section:

  • Trichophyton rubrum
advertisement

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to evaluate the carcinogenic potential of Benecut Cream have not been performed.

Benecut revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster ovary cell chromosome aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus assay).

Oral administration of Benecut to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 100 mg/kg/day (6.1 times MRHD).

14 CLINICAL STUDIES

14.1 Tinea Cruris

Benecut Cream has been investigated for safety and efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 146 subjects with symptomatic and dermatophyte culture positive tinea cruris. Subjects were randomized to receive Benecut Cream or vehicle. Subjects applied Benecut Cream or vehicle to the affected area plus a ½-inch margin of healthy skin surrounding the affected area once-daily for 2 weeks. Signs and symptoms of tinea cruris were assessed, and KOH examination and dermatophyte culture were performed at the primary efficacy endpoint at week 4.

The mean age of the trial population was 47 years and 87% were male and 43% were white. At baseline, subjects were confirmed to have signs and symptoms of tinea cruris, positive KOH exam, and confirmed dermatophyte presence based on culture results from a central mycology laboratory. The analysis of the intent-to-treat population was a comparison of the proportions of subjects with a complete cure at the week 4 visit. Complete cure was defined as both clinical cure (absence of erythema, pruritus, and scaling) and mycological cure (negative KOH and dermatophyte culture).

The percentage of subjects experiencing clinical cure and the percentage of subjects experiencing mycological cure at week 4 are presented individually in Table 1 below.

Endpoint Benecut Cream, 2%

N=75

Vehicle

N=71

Complete CureComplete cure is a composite endpoint of both mycological cure and clinical cure.

Clinical cure is defined as the absence of erythema, pruritus, and scaling (grade of 0).

19 (25%) 2 (3%)
Effective TreatmentEffective treatment is a negative KOH preparation and negative dermatophyte culture, erythema, scaling, and pruritus grades of 0 or 1 (absent or nearly absent). 45 (60%) 7 (10%)
Mycological CureMycological cure is defined as negative KOH and dermatophyte culture. 54 (72%) 11 (16%)

14.2 Interdigital Tinea Pedis

Benecut Cream has been investigated for efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 217 subjects with symptomatic and dermatophyte culture positive interdigital tinea pedis. Subjects were randomized to receive Benecut Cream or vehicle. Subjects applied Benecut Cream or vehicle to the affected area of the foot plus a ½-inch margin of healthy skin surrounding the affected area once-daily for 2 weeks. Signs and symptoms of interdigital tinea pedis (presence or absence of erythema, pruritus, and scaling) were assessed and KOH examination and dermatophyte culture was performed at the primary efficacy endpoint at week 6.

The mean age of the trial population was 42 years and 71% were male and 57% were white. At baseline, subjects were confirmed to have signs and symptoms of interdigital tinea pedis, positive KOH exam, and confirmed dermatophyte culture. The primary efficacy endpoint was the proportions of subjects with a complete cure at the week 6 visit. Complete cure was defined as both a clinical cure (absence of erythema, pruritis, and scaling) and mycological cure (negative KOH and dermatophyte culture).

The efficacy results at week 6, four weeks following the end of treatment, are presented in Table 2 below. Benecut Cream demonstrated complete cure in subjects with interdigital tinea pedis, but complete cure in subjects with only moccasin type tinea pedis was not demonstrated.

Endpoint Benecut Cream, 2%

N=147

Vehicle

N=70

Complete CureComplete cure is a composite endpoint of both mycological cure and clinical cure.

Clinical cure is defined as absence of erythema, pruritus, and scaling (grade of 0).

26 (18%) 5 (7%)
Effective TreatmentEffective treatment is a negative KOH preparation and negative dermatophyte culture, erythema, scaling, and pruritus grades of 0 or 1 (absent or near absent). 83 (57%) 14 (20%)
Mycological CureMycological cure is defined as negative KOH and dermatophyte culture. 99 (67%) 15 (21%)

14.3 Tinea Corporis

Naftifine Hydochloride Cream has been investigated for safety and efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 184 subjects with symptomatic and dermatophyte culture positive tinea corporis. Subjects were randomized to receive Benecut Cream or vehicle. Subjects applied the study agent to all affected body surface areas with tinea corporis plus a ½ inch margin of healthy skin surrounding the affected lesions for two weeks. Signs and symptoms of tinea corporis (presence or absence of erythema, induration, and pruritus) were assessed and KOH examination and dermatophyte culture were performed for the assessment of primary efficacy endpoint at Day 21.

The trial population was pediatric (≥2 to <18 years of age) with a median age of 9 years (Naftifine Hydrochloride Cream) or 8 years (vehicle); 61% of subjects were male and 45% were white. At baseline, subjects were confirmed to have signs and symptoms of tinea corporis, positive KOH exam, and confirmed dermatophyte culture. The primary efficacy endpoint was the proportions of subjects with a complete cure at the Day 21 visit. Complete cure was defined as both a clinical cure (absence of erythema, induration, and pruritus on all lesions present at baseline) and mycological cure (negative KOH and dermatophyte culture).

The efficacy results at Day 21, one week following the end of treatment, are presented in Table 3 below.

Endpoint Benecut Cream, 2%

N=91

Vehicle

N=93

Complete CureComplete cure is a composite endpoint of both mycological cure and clinical cure.

Clinical cure is defined as absence of erythema, pruritus, and scaling (grade of 0).

42 (46%) 26 (28%)
Effective TreatmentEffective treatment is a negative KOH preparation and negative dermatophyte culture, erythema, induration, and pruritus grades of 0 or 1 (absent or mild). 53 (58%) 32 (34%)
Mycological CureMycological cure is defined as negative KOH and dermatophyte culture. 57 (63%) 36 (39%)

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Benecut Cream USP, 2% is a white to off-white cream supplied in tubes in the following sizes:

30 g – NDC 51672-1368-2

45 g – NDC 51672-1368-6

60 g – NDC 51672-1368-3

Storage: Store Benecut Cream USP, 2% at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

  • Inform patients that Benecut Cream is for topical use only. Benecut Cream is not intended for oral, intravaginal or ophthalmic use.
  • If irritation or sensitivity develops with the use of Benecut Cream treatment should be discontinued and appropriate therapy instituted. Patients should be directed to contact their physician if these conditions develop following use of Benecut Cream.

Manufactured by: Taro Pharmaceuticals Inc.

Brampton, Ontario, Canada L6T 1C1

Distributed by: Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

Revised: January, 2017

PK-7472-1

0117-1

115

Benecut pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Benecut available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Benecut destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Benecut Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Benecut pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."NAFTIFINE HYDROCHLORIDE CREAM [TARO PHARMACEUTICALS U.S.A., INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Benecut?

Depending on the reaction of the Benecut after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Benecut not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Benecut addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Benecut, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Benecut consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 11 here

The information was verified by Dr. Arunabha Ray, MD Pharmacology

© 2002 - 2021 "sdrugs.com". All Rights Reserved