LUDURA Cream / Lotion (Luliconazole)

Table of Content

Tinea infections are superficial fungal infections caused by dermatophytes. They are a group of fungi that invade and grow in dead keratin and produce a ring-like pattern - hence the term 'ringworm'. They affect skin, hair and nails.

Luliconazole is a broad spectrum antifungal with activity against a variety of etiologic fungi in skin infections. Luliconazole is an imidazole class drug (which has 2 ring nitrogens in a 5-membered ring). Luliconazole bears a second meta-substituted chlorine on its benzene ring, which enhances the potency of luliconazole

Luliconazole disrupts ergosterol synthesis by inhibiting the enzyme lanosterol demethylase. This results in decreased amounts of ergosterol, a constituent of fungal cell membranes, and a corresponding accumulation of lanosterol which ultimately leads to inhibition of cell growth. Imidazoles also alter the synthesis of triglycerides and phospholipids, which leads to an accumulation of toxic levels of hydrogen peroxide within fungal cells. This build-up of toxic concentrations of hydrogen peroxide may contribute to the deterioration of the cell and cell death.

LUDURA contains luliconazole 1% in the form of cream and lotion.  It is indicated for the treatment of tinea cruris, tinea corporis and tinea pedis. LUDURA cream is available in pack of 20 gm and LUDURA lotion is available in pack of 30 ml.

May 2017

Composition

LUDURA Cream

Luliconazole…………………………………..1.0% w/w 

LUDURA Lotion

Luliconazole…………………………………..1.0% w/w 

Dosage Form

Cream and lotion

Pharmacology

Pharmacodynamics

Luliconazole is an antifungal that belongs to the azole class. Although the exact mechanism of action against dermatophytes is unknown, luliconazole appears to inhibit ergosterol synthesis by inhibiting the enzyme lanosterol demethylase. Inhibition of this enzyme’s activity by azoles results in decreased amounts of ergosterol, a constituent of fungal cell membranes, and a corresponding accumulation of lanosterol.

Pharmacokinetics

Luliconazole is the R-enantiomer of a chiral molecule. The potential for interconversion between R- and S-enantiomers in humans has not been assessed. Information on the pharmacokinetics of luliconazole presented below refers to both the R-enantiomer and S-enantiomer, if any, combined. Luliconazole is >99% protein-bound in plasma.

In a pharmacokinetic trial, 12 subjects with moderate-to-severe tinea pedis and 8 subjects with moderate-to-severe tinea cruris applied a mean daily amount of approximately 3.5 grams of luliconazole cream, 1%, to the affected and surrounding areas once daily for 15 days. Plasma concentrations of luliconazole on day 15 were measurable in all subjects and fluctuated little during the 24-hour interval. In subjects with tinea pedis, the mean ± SD of the maximum concentration (Cmax) was 0.40 ± 0.76 ng/mL after the first dose and

0.93 ± 1.23 ng/mL after the final dose. The mean time to reach Cmax (Tmax) was 16.9 ± 9.39 hours after the first dose and 5.8 ± 7.61 hours after the final dose. Exposure to luliconazole, as expressed by area under the concentration time curve (AUC0–24) was 6.88 ± 14.50 ng*hr/mL after the first dose and 18.74 ± 27.05 ng*hr/mL after the final dose. In subjects with tinea cruris, the mean ± SD Cmax was 4.91 ± 2.51 ng/mL after the first dose and 7.36 ± 2.66 ng/mL after the final dose. The mean Tmax was 21.0 ± 5.55 hours after the first dose and 6.5 ± 8.25 hours after the final dose. Exposure to luliconazole, as expressed by AUC0– 24, was 85.1 ± 43.69 ng*hr/mL after the first dose and 121.74 ± 53.36 ng*hr/mL after the final dose.

Indications

LUDURA is indicated for the topical treatment of cutaneous mycosis, i.e tinea pedis, tinea cruris, and tinea corporis in patients 18 years of age and older.

Dosage and Administration

For topical use only. LUDURA is not for ophthalmic, oral, or intravaginal use.

  • ·         When treating tinea pedis, a thin layer of LUDURA should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for 2 weeks.
  • ·         When treating tinea cruris or tinea corporis, LUDURA should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for 1 week.

Contraindications

LUDURA is contraindicated in patients who have demonstrated hypersensitivity to luliconazole or any of the inactive ingredients of the formulation.

Warnings and Precautions

LUDURA is for external use only, avoid contact with eyes.  Do not apply to the cornea and conjunctiva as ophthalmic use. Do not apply to the areas with marked erosion/fissures.

Drug Interactions

An in vivo study in adult subjects with moderate-to-severe interdigital tinea pedis and tinea cruris showed that luliconazole cream, 1%, is a weak inhibitor of CYP2C19.

Results of in vitro studies indicated that therapeutic doses of luliconazole cream, 1%, do not inhibit cytochrome P450 (CYP) enzymes 1A2, 2C9 and 2D6, but can inhibit the activity of CYP2B6, 2C8, 2C19, and 3A4. CYP2C19, the most sensitive enzyme, was further evaluated in an in vivo study using omeprazole as a probe substrate in adult subjects with moderate-to-severe interdigital tinea pedis and tinea cruris. The results showed that luliconazole cream, 1%, applied at a daily amount of approximately 4 grams increased the omeprazole systemic exposure (AUC) by approximately 30% compared to the exposure of omeprazole administered alone. Luliconazole cream, 1%, is considered a weak inhibitor of CYP2C19.

Results of in vitro studies indicated that therapeutic doses of luliconazole cream, 1%, did not induce CYP1A2, 2B6, and 3A4.

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of luliconazole 1%, in pregnant women. It should be used during pregnancy only if potential benefit justifies the potential risk to the foetus.

Lactation

It is not known whether luliconazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when luliconazole 1% is prescribed to women who are breastfeeding.

Paediatric Use

The safety and effectiveness of luliconazole 1% in paediatric patients has not been established.

Geriatric Use

No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Undesirable Effects

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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In the pre-approval clinical studies, incidence of reported adverse reactions was 2.5% (28 cases, 36 events) of the 1,142 patients (1,035 for the cream, 107 for solution). All of the main adverse reactions were localized to the application sites. The data of adverse events is presented in the table below.

If the following symptoms occur, appropriate measures, including discontinuation should be taken.

Table 1: Incidence of adverse events

 

≥0.1% to >5%

<0.1%

Unknown

Cream

Dermatologic

Itching (0.7%), redness (0.6%), irritation (0.5%), contact dermatitis (0.5%), pain (0.4%), and eczema (0.2%)

Hot flush, heat sensation and burning sensation

Vesicle*

Other

 

Increase in BUN and increase in urinary protein 

 

Solution

Dermatologic

Irritation (0.9%) and contact dermatitis (0.9%)

 

Itching*

*Incidence rate is unknown, due to voluntary report

In other three Phase 3 clinical trials, 616 subjects were exposed to luliconazole cream, 1%: 305 with interdigital tinea pedis and 311 subjects with tinea cruris. Subjects with interdigital tinea pedis or tinea cruris applied luliconazole cream, 1%, or vehicle cream once daily for 14 days or 7 days, respectively, to the affected and adjacent areas. During clinical trials with luliconazole cream, 1%, the most common adverse reactions were application site reactions, which occurred in less than 1% of subjects in both the luliconazole cream and vehicle arms. Most adverse reactions were mild in severity.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of luliconazole cream, 1%: contact dermatitis and cellulitis. 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.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024.  

By reporting side effects you can help provide more information on the safety of this product.

Overdosage

Not reported.

Shelf-Life

2 years

Storage and Handling Instructions

Store at a temperature not exceeding 25⁰C. Do not freeze. Protect from light.

Packaging Information

LUDURA Cream: Available in a 20 g tube

LUDURA Lotion: Available in a 30 ml tube

Last Updated: May 2017

Last Reviewed: May 2017