PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Topical Dermatological Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Topical azole antifungal cream
    Used for tinea pedia, tinea cruris, and tinea corporis
    FDA-approved in adults and pediatric patients 12 years and older for tinea pedia and tinea cruris and in adults and pediatric patients 2 years and older for tinea corporis

    COMMON BRAND NAMES

    LUZU

    HOW SUPPLIED

    Luliconazole/LUZU Topical Cream: 1%

    DOSAGE & INDICATIONS

    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

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed.

    Renal Impairment

    No dosage adjustment is needed.

    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.

    STORAGE

    LUZU:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Azole antifungals hypersensitivity

    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.

    Ocular exposure, ophthalmic administration

    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.

    Pregnancy

    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).

    Breast-feeding

    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.

    ADVERSE REACTIONS

    Moderate

    contact dermatitis / Delayed / Incidence not known

    Mild

    skin irritation / Early / 0-1.0

    DRUG INTERACTIONS

    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: (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; 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.
    Carbetapentane; 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.
    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; Hydrocodone; 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.
    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.
    Etravirine: (Moderate) Theoretically, luliconazole may increase the side effects of etravirine, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of etravirine, such as rash. 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.
    Lansoprazole; Naproxen: (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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.

    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.