Luliconazole is a topical azole antifungal cream indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum or Epidermophyton floccosum. It is approved in adult and pediatric patients 12 years and older for tinea pedis and tinea cruris and in adult and pediatric patients 2 years and older for tinea corporis. In tinea pedis studies in adults, complete clearance (defined as clinical cure and mycological cure) at 4 weeks post-treatment was achieved in 26% and 14% of luliconazole recipients compared to 2% and 3% of patients receiving the vehicle cream. Similar results were observed in the tinea cruris study with 21% of patients receiving the active drug and 4% of patients receiving the vehicle cream achieving complete clearance at 3 weeks post-treatment. In the tinea corporis study in pediatric patients 2 years and older, complete clearance (defined as clinical cure and mycological cure) at 3 weeks post-treatment was achieved in 71% of luliconazole recipients compared to 36% of patients receiving the vehicle cream.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-For topical dermatologic use only; not for ophthalmic, oral, or intravaginal use.
Cream/Ointment/Lotion Formulations
-Wash hands before and after application.
-Rub cream gently into the affected area(s). Apply an amount sufficient to cover the affected area and 1 inch of the immediate surrounding skin. Avoid getting in the eyes, nose, mouth, or other mucous membranes.
Application site reactions (i.e., skin irritation) were observed in < 1% of patients treated with luliconazole during clinical trials. An evaluation of these reactions showed most were mild in severity. Cases of contact dermatitis and cellulitis have been noted with post-marketing use.
Luliconazole is an azole antifungal; avoid use in patients with a history of azole antifungals hypersensitivity. Instruct patients to discontinue use of the drug and seek immediate medical attention if a hypersensitivity reaction develops during treatment.
Avoid ocular exposure to luliconazole; do not administer by ophthalmic administration. If ocular exposure occurs, treat by immediately flushing the affected eye with cool, clean water.
No adequate and controlled studies have been conducted to evaluate use of luliconazole in pregnant women; administer during pregnancy only if the potential benefits to the mother justify the possible risks to the fetus. Animal studies were conducted in rats and rabbits; multiples of human exposure calculations were based on human daily dose body surface area comparisons (mg/m2) for the reproductive toxicology studies. The Maximum Recommended Human Dose (MRHD) was set at 8 g 1% cream per day (1.33 mg/kg/day for a 60 kg individual is equivalent to 49.2 mg/m2/day). In pregnant rats, subcutaneous doses of 1, 5, and 25 mg/kg/day were administered during organogenesis. At 25 mg/kg/day (3-times the MRHD based on BSA comparisons), no treatment related effects on maternal toxicity or malformations were noted, but there were increased incidences of skeletal variation (14th rib) in the pups. The manufacturer notes that when there was maternal toxicity present at 25 mg/kg/day, embryofetal toxicity (increased prenatal pup mortality, reduced live litter sizes and increased postnatal pup mortality) was observed. In rats, there were no treatment related effects on skeletal variation or embryofetal toxicity at 5 mg/kg/day (0.6-times the MRHD based on BSA comparisons). In pregnant rabbits, no treatment related effects on maternal toxicity, embryofetal toxicity or malformations were seen at doses up to 100 mg/kg/day (24-times the MRHD based on BSA comparisons).
It is not known if luliconazole is excreted in human milk. According to the manufacturer, caution is advised when administering to women who are breast-feeding. Fluconazole, clotrimazole, and miconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Epidermophyton floccosum, Trichophyton rubrum
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of interdigital tinea pedis:
Topical dosage:
Adults: Apply a thin layer of cream topically to affected areas, and approximately 1 inch of the immediate surrounding areas, once daily for 2 weeks.
Children and Adolescents 12 to 17 years: Apply a thin layer of cream topically to affected areas, and approximately 1 inch of the immediate surrounding areas, once daily for 2 weeks.
For the treatment of tinea cruris:
Topical dosage:
Adults: Apply topically to affected areas, and approximately 1 inch of the immediate surrounding areas, once daily for 1 week.
Children and Adolescents 12 to 17 years: Apply topically to affected areas, and approximately 1 inch of the immediate surrounding areas, once daily for 1 week.
For the treatment of tinea corporis:
Topical dosage:
Adults: Apply topically to affected areas, and approximately 1 inch of the immediate surrounding area, once daily for 1 week.
Children and Adolescents 2 to 17 years: Apply topically to affected areas, and approximately 1 inch of the immediate surrounding area, once daily for 1 week.
Maximum Dosage Limits:
-Adults
Specific maximum dosage information is not available.
-Geriatric
Specific maximum dosage information is not available.
-Adolescents
Specific maximum dosage information is not available.
-Children
2 to 12 years: Specific maximum dosage information is not available.
younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Acetaminophen; Diphenhydramine: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Theoretically, luliconazole may increase the side effects of carisoprodol, which is a CYP2C19 substrate. Monitor patients for adverse effects of carisoprodol, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Aspirin, ASA; Omeprazole: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Atovaquone; Proguanil: (Minor) Theoretically, luliconazole may increase the side effects of atovaquone; proguanil, as proguanil is a CYP2C19 substrate. Monitor patients for adverse effects of proguanil, such as GI and CNS effects. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of topical luliconazole with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and topical luliconazole is a CYP2C19 inhibitor.
Bortezomib: (Moderate) Theoretically, luliconazole may increase the side effects of bortezomib, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of bortezomib, such as peripheral neuropathy, hematologic toxicities, and GI events. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Carisoprodol: (Moderate) Theoretically, luliconazole may increase the side effects of carisoprodol, which is a CYP2C19 substrate. Monitor patients for adverse effects of carisoprodol, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Cilostazol: (Moderate) Theoretically, luliconazole may increase the side effects of cilostazol, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of cilostazol, such as increased bleeding. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Citalopram: (Moderate) Theoretically, luliconazole may increase the side effects of citalopram, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of citalopram, such as QT prolongation, serotonin syndrome, and neuroleptic malignant syndrome. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Clomipramine: (Moderate) Theoretically, luliconazole may increase the side effects of clomipramine, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of clomipramine, such as QT prolongation, CNS effects, or antimuscarinic effects. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Clopidogrel: (Minor) Monitor for reduced clopidogrel efficacy during concomitant use of luliconazole. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19. In vitro, luliconazole is a CYP2C19 inhibitor and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. However, no in vivo drug interaction trials have been conducted to evaluate the effect of luliconazole on drugs that are substrates of CYP2C19.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Diazepam: (Moderate) Theoretically, luliconazole may increase the side effects of diazepam, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of diazepam, such as CNS effects and respiratory depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Diphenhydramine: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Diphenhydramine; Ibuprofen: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Diphenhydramine; Naproxen: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Diphenhydramine; Phenylephrine: (Moderate) Theoretically, luliconazole may increase the side effects of diphenhydramine, which is a CYP2C19 substrate. Monitor patients for adverse effects of diphenhydramine, such as CNS depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Doxepin: (Moderate) Theoretically, luliconazole may increase the side effects of doxepin, which is a CYP2C19 substrate. Monitor patients for adverse effects of doxepin, such as CNS effects and cardiovascular events. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Escitalopram: (Moderate) Theoretically, luliconazole may increase the side effects of escitalopram, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of escitalopram, such as GI effects or serotonin sydrome. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Esomeprazole: (Minor) Theoretically, luliconazole may increase the side effects of esomeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of exomeprazole, such as GI events. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Imipramine: (Moderate) Theoretically, luliconazole may increase the side effects of imipramine, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of imipramine, such as CNS and cardiovascular effects. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lacosamide: (Moderate) Theoretically, luliconazole may increase the side effects of lacosamide, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of lacosamide, such as PR prolongation. Patients with renal or hepatic impairment may be particularly affected. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lansoprazole: (Minor) Theoretically, luliconazole may increase the side effects of lansoprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of lansoprazole, such as electroylyte changes. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 amd CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Theoretically, luliconazole may increase the side effects of lansoprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of lansoprazole, such as electroylyte changes. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 amd CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting topical luliconazole therapy. Avoid initiation of topical luliconazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable topical luliconazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and topical luliconazole is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Methadone: (Moderate) Theoretically, luliconazole may increase the side effects of methadone, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of methadone, such as CNS and respiratory depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Naproxen; Esomeprazole: (Minor) Theoretically, luliconazole may increase the side effects of esomeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of exomeprazole, such as GI events. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Omeprazole: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Omeprazole; Sodium Bicarbonate: (Minor) Theoretically, luliconazole may increase the side effects of omeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of omeprazole. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Oxybutynin: (Moderate) Theoretically, luliconazole may increase the side effects of oxybutynin, which is a CYP (2C19 or 3A4) substrate. Monitor patients for adverse effects of oxybutynin, such as CNS and anticholinergic effects. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP (2C19 or 3A4) and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Propafenone: (Moderate) The manufacturer of propafenone warns that it should be used with caution with drugs that inhibit CYP1A2 and CYP3A4, which could theoretically reduce metabolism of propafenone to N-depropylpropafenone. N-depropylpropafenone is formed via dual metabolic pathways (CYP1A2 and/or CYP3A4). Drugs that inhibit CYP1A2 and CYP3A4 can be expected to increase the serum concentrations of propafenone. When propafenone is coadministered with inhibitors of CYP1A2 or CYP3A4, the patients should be closely monitored and the dosage of propafenone adjusted as needed to meet therapeutic goals. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Quinine: (Moderate) Theoretically, luliconazole may increase the side effects of quinine, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of quinine, such as QT prolongation and cinchonism. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Rabeprazole: (Minor) Theoretically, luliconazole may increase the side effects of rabeprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of rabeprazole, such as GI effects. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering luliconazole. Although this interaction has not been studied by the manufacturer and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4. In vitro data suggest luliconazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
Voriconazole: (Moderate) Theoretically, luliconazole may increase the side effects of voriconazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of voriconazole, such as visual impairment, elevated hepatic enzymes, and QT prolongation. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Warfarin: (Moderate) Theoretically, luliconazole may increase the side effects of warfarin, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of warfarin, such as increased bleeding, PT, and INR. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Ziprasidone: (Moderate) Theoretically, luliconazole may increase the side effects of ziprasidone, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of ziprasidone, such as QT prolongation, CNS effects, and extrapyramidal symptoms. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
The exact mechanism of action is unknown; however, luliconazole may exert its antifungal activity by disrupting normal fungal cell membrane permeability. Luliconazole and other azole antifungal agents inhibit lanosterol desmethylase in susceptible fungi, which leads to a decrease in ergosterol concentration and accumulation of lanosterol.
Luliconazole is administered topically. After systemic absorption, the drug is more than 99% bound to plasma proteins. Distribution, metabolism, and excretion data are not available.
Affected cytochrome P450 isoenzymes: CYP2C19, CYP3A4, CYP2C8, CYP2B6
Data from an in vitro study indicated that luliconazole, at therapeutic doses, may inhibit the activity of CYP2C19, CYP3A4, CYP2C8, and CYP2B6. The isoenzyme most susceptible to inhibition by luliconazole, CYP2C19, was further evaluated in an in vivo drug interaction study using omeprazole as a probe substrate. Data from this study found 4 grams per day of luliconazole applied topically increased the systemic exposure of omeprazole by 30%. Luliconazole is considered a weak CYP2C19 inhibitor; however for tinea cruris, extrapolation from both in vitro inhibition studies and in vivo data in adults to adolescent subjects showed that in some patients, concentrations of luliconazole can approach or exceed those required to be a moderate inhibitor of CYP2C19.
-Route-Specific Pharmacokinetics
Topical Route
Pharmacokinetic parameters were evaluated in 12 patients with moderate to severe tinea pedis and 8 patients with moderate to severe tinea cruris. After 15 days of treatment, plasma concentrations were measurable in all patients and the maximum concentration (Cmax), time to reach maximum concentration (Tmax), and exposure (AUC) were recorded. In patients with tinea pedis, the mean Cmax after the first and last doses were 0.4 +/- 0.76 ng/mL and 0.93 +/- 1.23 ng/mL, the mean Tmax after the first and last doses were 16.9 +/- 9.39 hours and 5.8 +/- 7.61 hours, and the mean AUC after the first and last doses were 6.88 +/- 14.5 ng x hour/mL and 18.74 +/- 27.05 ng x hour/mL. For patients with tinea cruris, the respective mean Cmax, Tmax, and AUC after the first and last doses were 4.91 +/- 2.51 ng/mL and 7.36 +/- 2.66 ng/mL, 21 +/- 5.55 hours and 6.5 +/- 8.25 hours, and 85.1 +/- 43.69 ng x hour/mL and 121.74 +/- 53.36 ng x hour/mL.
-Special Populations
Pediatrics
The pharmacokinetics of luliconazole were assessed in 30 adolescent patients (12 to 17 years) with moderate to severe tinea pedis (n = 15) or tinea cruris (n = 15). In general, the systemic exposure of luliconazole was greater in subjects with tinea cruris than tinea pedis. In patients with tinea cruris, the mean Cmax after the first and last dose (day 8) was 9.8 and 15.4 ng/mL, respectively. The mean AUC after the first and last dose was 157.07 and 266.06 ng x hour/mL, respectively. In patients with tinea pedis, the mean Cmax after the first and last dose (day 15) was 1.8 and 3.27 ng/mL, respectively. The mean AUC after the first and last dose was 20.47 and 60.38 ng x hour/mL, respectively.