Luliconazole

Luliconazole is a Topical Antifungal Agent belonging to the pharmacological class of Azole antifungals.

Luliconazole has been approved to relieve symptoms and also for the treatment and maintenance of Tinea Corporis/Tinea Cruris, Tinea Pedis .

Luliconazole, an antifungal medication applied topically, exhibits a maximum plasma concentration of 0.40 ± 0.76 ng/mL (mean ± SD) approximately 16.9 ± 9.39 hours (mean ± SD) after the first dose in patients with tinea pedis, as indicated by clinical studies. The volume of distribution for luliconazole has not been quantified. Notably, over 99% of luliconazole in plasma is bound to proteins. Regarding metabolism, specific details have not yet been determined. Additionally, the route of elimination for luliconazole remains unknown at this time. Further research and investigation are needed to better understand these aspects of luliconazole's pharmacokinetics.

The common side effects of Luliconazole include Skin irritation or itching at the site of apllictaion, Redness or rash at the application site, Peeling or dryness of the skin, Burning or stinging sensation at the application site.

Luliconazole is available in the form of Topical Cream.

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

Luliconazole, belonging to the pharmacological class of Azole antifungals, acts as a Topical Antifungal Agent.

While the precise mechanism of action for luliconazole's antifungal activity remains unclear, it is believed to involve the inhibition of the enzyme lanosterol demethylase. Lanosterol demethylase plays a crucial role in the synthesis of ergosterol, a vital component of fungal cell membranes. By interfering with this enzyme, luliconazole likely disrupts the production of ergosterol, ultimately compromising the integrity and function of the fungal cell membranes. This disruption contributes to the antifungal effect of luliconazole, helping to combat fungal infections effectively.

Luliconazole has been approved to relieve symptoms and also for the treatment and maintenance of Tinea Corporis/Tinea Cruris, Tinea Pedis .

Luliconazole is found to be available in the form of Topical Cream.

Luliconazole can be used in the following treatment:

• Tinea Corporis/Tinea Cruris
• Tinea Pedis

Luliconazole can help to relieve symptoms and also for the treatment and maintenance of Tinea Corporis/Tinea Cruris, Tinea Pedis.

Luliconazole is approved for use in the following clinical indications:

• Tinea Corporis/Tinea Cruris
• Tinea Pedis

Tinea Infections: Topical Treatment Guidelines

Tinea Corporis/Tinea Cruris:

• Topical Cream: Apply to affected and surrounding area(s) once daily until clinical resolution, typically 1 to 3 weeks .

Tinea Pedis (Labeled Use)/Tinea Manuum (Off-Label Use):

• Topical Cream: Apply to affected and surrounding area(s) once daily until 1 week after clinical resolution, typically for 2 to 4 weeks in total .

Tinea infections, such as tinea corporis (ringworm) and tinea cruris (jock itch), can be effectively treated using topical creams. For these conditions, the cream should be applied to the affected and surrounding area(s) once daily until clinical resolution is achieved, typically within 1 to 3 weeks. Similarly, in the case of tinea pedis (athlete's foot) with labelled use and tinea manuum (fungal infection of the hand) with off-label use, the topical cream application is recommended once daily until 1 week after the clinical resolution, typically requiring treatment for 2 to 4 weeks in total. Adhering to these topical treatment guidelines can help effectively manage and resolve tinea infections.

Luliconazole is available in the following dosage forms and strengths:

• Topical Cream: 1%

Topical Cream

• Dosage Adjustments in Kidney Patients:

There are found to be no dosage adjustments in the manufacturer's labelling.

• Dosage Adjustments in Hepatic Impairment Patients:

There are found to be no dosage adjustments in the manufacturer's labelling.

• Dosage Adjustments in Pediatric Patients:

Fungal Infections: Topical Treatment Recommendations

Tinea Pedis and Tinea Cruris:

• Children ≥12 years and Adolescents: Apply to affected and surrounding area(s) once daily until clinical resolution, typically 1 to 3 weeks

Tinea Corporis:

• Children ≥2 years and Adolescents: Apply to affected and surrounding area(s) once daily until clinical resolution, typically 1 to 3 weeks

Fungal infections, such as tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm), can be effectively treated with topical medications. In cases involving children aged 12 years and older and adolescents, the dosing recommendations for topical treatment are the same as those for adults. Additionally, for tinea pedis and tinea cruris, children aged 2 years and older and adolescents can also follow the adult dosing guidelines. Proper adherence to these treatment recommendations can help manage and resolve fungal infections effectively.

When taking Luliconazole, there are certain dietary restrictions that should be followed to ensure the medication's effectiveness and safety:

• There are found to be no specific dietary restrictions associated with the use of Luliconazole. However, it is generally recommended to take Luliconazole with water and not with grapefruit juice or milk, as these substances may interfere with the drug's absorption or metabolism.
• There are no specific dietary restrictions related to the use of luliconazole. Luliconazole is a topical antifungal medication that is applied to the skin, and it is not intended to be ingested. Therefore, there are no dietary interactions with food that are known to affect the use or efficacy of luliconazole.

The dietary restriction should be individualized as per patient requirements.

Luliconazole may be contraindicated under the following conditions:

• Hypersensitivity to the active substance Luliconazole or to any of the excipients.

Patient Information and Proper Use Instructions:

Advise the patient to carefully read the FDA-approved patient labeling (Patient Information) provided with Luliconazole. Emphasize that Luliconazole is intended for topical use only and should not be used intravaginally or in the eyes.

Nonclinical Toxicology:

Carcinogenicity, Mutagenicity, and Fertility:

Long-term studies assessing the potential carcinogenicity of Luliconazole have not been conducted.

Based on various tests conducted on luliconazole, including the Ames assay, Chinese hamster lung cell chromosomal aberration assay, and mouse bone marrow micronucleus test, there is no evidence of any harmful mutagenic or clastogenic potential. However, a study conducted on rats showed that subcutaneous administration of luliconazole before and during mating and early pregnancy resulted in treatment-related effects. Females exhibited decreased live embryos and corpus luteum at doses of 5 and 25 mg/kg/day, while males showed decreased sperm counts at 25 mg/kg/day. It is important to note that no treatment-related effects on fertility or reproductive function were observed at a dose of 1 mg/kg/day, which is equal to 0.1 times the Maximum Recommended Human Dose based on the body surface area comparisons.

The excretion of luliconazole in human milk is not known. Since several drugs are known to be excreted in human milk, caution should be exercised when administering Luliconazole to breastfeeding women.

Pregnancy:

Pregnancy Category C.

It is important to note that there haven't been enough studies conducted to determine the effects of Luliconazole on pregnant women. Therefore, it should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus.

To determine the effects of Luliconazole, subcutaneous doses were given to pregnant rats and rabbits during the period of organogenesis. In rats, a dose of 25 mg/kg/day (which is 3 times more than the Maximum Recommended Human Dose [MRHD] based on BSA comparisons) did not cause any treatment-related effects on maternal toxicity or malformations, but there were increased incidences of skeletal variation. Meanwhile, in rabbits, a 100 mg/kg/day dose (which is 24 times more than the MRHD based on BSA comparisons) also did not cause any treatment-related effects on maternal toxicity, embryofetal toxicity, or malformations.

During organogenesis through the end of lactation, rats were administered subcutaneous doses of 1, 5, and 25 mg/kg/day. Embryofetal toxicity was observed in the presence of maternal toxicity at a 25 mg/kg/day dose. However, at a 5 mg/kg/day dose (which is 0.6 times the MRHD based on BSA comparisons), no embryo-fetal toxicity was observed. Postnatal development was not affected at 25 mg/kg/day (which is 3 times the MRHD based on BSA comparisons).

There are certain food-related warnings and precautions to consider when using Luliconazole:

• There are no specific food warnings related to the use of luliconazole. Luliconazole is a topical antifungal medication that is applied to the skin, and it is not intended to be ingested. Therefore, there are no dietary restrictions or interactions with food that are known to affect the use or efficacy of luliconazole.

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

Common:

• Skin irritation at the site of application
• Redness or rash at the application site
• Peeling or dryness of the skin
• Burning sensation at the site of application

Less common:

• Allergic reactions, such as hives or difficulty breathing
• Swelling of the face, lips, tongue, or the throat

The clinically relevant drug interactions of Luliconazole are briefly summarized here

• In vitro evaluations were conducted to assess the potential of luliconazole to inhibit cytochrome P-450 (CYP) enzymes 1A2, 2C9, 2C19, 2D6, and 3A4. The results indicate that at therapeutic doses, especially when applied to patients with moderate to severe tinea cruris, luliconazole may inhibit the activity of CYP2C19 and CYP3A4. However, there have been no in vivo drug interaction trials to assess the impact of luliconazole on other drugs that are substrates of CYP2C19 and CYP3A4.
• Based on the in vitro assessment, luliconazole is not expected to inhibit CYPs 1A2, 2C9, and 2D6. The induction potential of luliconazole on CYP enzymes has not been evaluated in available data.

The following are the side effects involving Luliconazole:

• Skin irritation at the site of application
• Redness or rash at the application site
• Peeling or dryness of the skin
• Burning sensation at the application site

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

Pregnancy:

Pregnancy Category C.

There have been no sufficient and controlled studies on the effects of Luliconazole in pregnant women. Therefore, it should only be used during pregnancy if the benefits outweigh the potential risks to the fetus.

For the calculations of animal multiples of human exposure, daily dose body surface area (BSA) comparisons (mg/m2) were used from reproductive toxicology studies on rats and rabbits. In rats, pregnant females were administered subcutaneous doses of 1, 5, and 25 mg/kg/day luliconazole during the period of organogenesis (gestational days 7-17). At 25 mg/kg/day (3 times the Maximum Recommended Human Dose [MRHD] based on BSA comparisons), no treatment-related effects on maternal toxicity or malformations were observed, though increased incidences of skeletal variation (14th rib) were noted. At 5 mg/kg/day (0.6 times the MRHD based on BSA comparisons), no treatment-related effects on skeletal variation were observed.

During the period of organogenesis (gestational days 6-18), pregnant female rabbits were given subcutaneous doses of luliconazole at levels of 4, 20, and 100 mg/kg/day. No harmful effects on maternal toxicity, embryofetal toxicity, or malformations were observed at the highest dose of 100 mg/kg/day (24 times the MRHD based on BSA comparisons).

During a study on rats' pre- and post-natal development, different doses of luliconazole were administered subcutaneously. The doses were 1 mg/kg/day, 5 mg/kg/day, and 25 mg/kg/day from gestation day 7 to lactation day 20. At the highest dose of 25 mg/kg/day, embryofetal toxicity was observed due to maternal toxicity, causing prenatal pup mortality, reduced live litter sizes, and increased postnatal pup mortality. However, no embryofetal toxicity was observed at the lower dose of 5 mg/kg/day. This dose is 0.6 times the MRHD, based on BSA comparisons. Additionally, the highest dose of 25 mg/kg/day, which is three times the MRHD based on BSA comparisons, did not have any adverse effects on postnatal development.

Lactation

The excretion of luliconazole in human milk is not known. Since several drugs are known to be excreted in human milk, caution is to be exercised when administering Luliconazole to breastfeeding women.

Pediatric

The safety and effectiveness of Luliconazole have not been established in pediatric patients. The number of pediatric patients aged 12 years and older was insufficient to adequately assess the safety and efficacy of the cream in this age group.

Geriatric Use

Among all the participants involved in clinical studies of Luliconazole, 8 per cent were aged 65 and over, and 1.4 per cent were aged 75 and over. Notably, no significant disparities were found in terms of safety or effectiveness between these elderly subjects and younger participants. Moreover, other clinical experiences reported also did not indicate any noteworthy distinctions in responses between the elderly and younger patients. However, it is essential to acknowledge that some older individuals may potentially exhibit greater sensitivity, although this cannot be definitively ruled out.

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

An overdose of luliconazole, a topical antifungal medication, is not a common occurrence due to its external application.

Pharmacodynamics:

Luliconazole effectively eliminates Trichophyton rubrum and Epidermophyton floccosum organisms, presumably by causing changes to their fungal cell membranes, leading to their destruction.

Pharmacokinetics:

● Absorption:

Following topical administration of luliconazole for tinea pedis, clinical studies have revealed that the first dose resulted in a maximum plasma concentration of 0.40 ± 0.76 ng/mL (mean ± SD) occurring in approximately 16.9 ± 9.39 hours (mean ± SD).

● Volume of Distribution:

The volume of distribution for luliconazole has not been quantified.

● Protein Binding:

Luliconazole exhibits high plasma protein binding, with more than 99% of the drug bound to plasma proteins.

● Metabolism:

The specific metabolic pathways of luliconazole have not been determined yet.

● Route of Elimination:

The route of elimination for luliconazole has not been established at this time.

1. https://reference.medscape.com/drug/luzu-luliconazole-999891
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204153s000lbl.pdf
3. https://go.drugbank.com/drugs/DB08933
4. https://www.rxlist.com/luzu-drug.htm
5. https://www.drugs.com/dosage/luliconazole-topical.html
6. https://pharmacy.services.conduent.com/mohealthnet/2014 6 June Drugs/6-14 PA Luzu.pdf