Ciclopirox

ADVERSE REACTIONS In the controlled clinical trial with 89 patients using ciclopirox topical suspension and 89 patients using the vehicle, the incidence of adverse reactions were low. Those considered possibly related to treatment or occurring in more than one patient were pruritus, which occurred in two patients using ciclopirox topical suspension and one patient using the suspension vehicle, and burning, which occurred in one patient using ciclopirox topical suspension.

CONTRAINDICATIONS Ciclopirox Topical Suspension USP is contraindicated in individuals who have shown hypersensitivity to any of its components.

DESCRIPTION Ciclopirox Topical Suspension USP, 0.77% is for topical use. Each gram of Ciclopirox Topical Suspension USP contains 7.70 mg of ciclopirox (as ciclopirox olamine) in a water miscible suspension base consisting of cetyl alcohol, cocamide DEA, lactic acid, mineral oil, myristyl alcohol, octyldodecanol, polysorbate 60, purified water, sorbitan monostearate, stearyl alcohol, and benzyl alcohol (1%) as preservative. Ciclopirox Topical Suspension USP contains a synthetic, broad-spectrum, antifungal agent ciclopirox (as ciclopirox olamine). The chemical name is 6-cyclohexyl-1-hydroxy-4-methyl-2(1 H )-pyridone, 2-aminoethanol salt. The CAS Registry Number is 41621-49-2. The chemical structure is: Ciclopirox Topical Suspension USP has a pH of 7. Chemical Structure

DOSAGE AND ADMINISTRATION Gently massage Ciclopirox Topical Suspension USP, 0.77% into the affected and surrounding skin areas twice daily, in the morning and evening. Clinical improvement with relief of pruritus and other symptoms usually occurs within the first week of treatment. If a patient shows no clinical improvement after four weeks of treatment with Ciclopirox Topical Suspension USP, the diagnosis should be redetermined. Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.

WARNINGS General Ciclopirox Topical Suspension USP is not for ophthalmic use. Keep out of reach of children.

CLINICAL PHARMACOLOGY Ciclopirox is a broad-spectrum, antifungal agent that inhibits the growth of pathogenic dermatophytes, yeasts, and Malassezia furfur . Ciclopirox exhibits fungicidal activity in vitro against isolates of Trichophyton rubrum , Trichophyton mentagrophytes , Epidermophyton floccosum , Microsporum canis , and Candida albicans . Pharmacokinetic studies in men with radiolabeled ciclopirox solution in polyethylene glycol 400 showed an average of 1.3% absorption of the dose when it was applied topically to 750 cm 2 on the back followed by occlusion for 6 hours. The biological half-life was 1.7 hours and excretion occurred via the kidney. Two days after application only 0.01% of the dose applied could be found in the urine. Fecal excretion was negligible. Autoradiographic studies with human cadaver skin showed that ciclopirox penetrates into the hair and through the epidermis and hair follicles into the sebaceous glands and dermis, while a portion of the drug remains in the stratum corneum. In vitro penetration studies in frozen or fresh excised human cadaver and pig skin indicated that the penetration of Ciclopirox Topical Suspension USP is equivalent to that of Ciclopirox Cream USP. Therapeutic equivalence of cream and suspension formulations also was indicated by studies of experimentally induced guinea pig and human trichophytosis.

20241219

4

Ciclopirox Ciclopirox BENZYL ALCOHOL CETYL ALCOHOL COCO DIETHANOLAMIDE LACTIC ACID, UNSPECIFIED FORM MINERAL OIL MYRISTYL ALCOHOL OCTYLDODECANOL POLYSORBATE 60 WATER SORBITAN MONOSTEARATE STEARYL ALCOHOL CICLOPIROX OLAMINE CICLOPIROX

Carcinogenesis, Mutagenesis, Impairment of Fertility A carcinogenicity study in female mice dosed cutaneously twice per week for 50 weeks followed by a 6-month drug-free observation period prior to necropsy revealed no evidence of tumors at the application site. The following in vitro and in vivo genotoxicity tests have been conducted with ciclopirox olamine: studies to evaluate gene mutation in the Ames Salmonella /Mammalian Microsome Assay (negative) and Yeast Saccharomyces Cerevisiae Assay (negative) and studies to evaluate chromosome aberrations in vivo in the Mouse Dominant Lethal Assay and in the Mouse Micronucleus Assay at 500 mg/kg (negative). The following battery of in vitro genotoxicity tests were conducted with ciclopirox: a chromosome aberration assay in V79 Chinese Hamster Cells, with and without metabolic activation (positive); a gene mutation assay in the HGPRT – test with V79 Chinese Hamster Cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA Synthesis Assay in A549 Human Cells (negative)). An in vitro Cell Transformation Assay in BALB/C3T3 Cells was negative for cell transformation. In an in vivo Chinese Hamster Bone Marrow Cytogenetic Assay, ciclopirox was negative for chromosome aberrations at 5000 mg/kg.

ANDA077092

Ciclopirox

Ciclopirox

51672-1323

HUMAN PRESCRIPTION DRUG

TOPICAL

PRINCIPAL DISPLAY PANEL - 60 mL Bottle Carton 60 mL NDC 51672-1323-4 Ciclopirox Topical Suspension USP, 0.77% (w/w) FOR DERMATOLOGIC USE ONLY. NOT FOR OPHTHALMIC USE. Bottle space provided to allow for vigorous shaking before each use. Keep this and all medications out of the reach of children. Rx only TARO PRINCIPAL DISPLAY PANEL - 60 mL Bottle Carton

Rx Only FOR DERMATOLOGIC USE ONLY NOT FOR OPHTHALMIC USE

Information for Patients The patient should be told to: Use the medication for the full treatment time even though signs/symptoms may have improved and notify the physician if there is no improvement after four weeks. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing) indicative of possible sensitization. Avoid the use of occlusive wrappings or dressings.

Nursing Mothers It is not known whether this drug is excreted in human milk. Caution should be exercised when Ciclopirox Topical Suspension USP, 0.77% is administered to a nursing woman.

Pediatric Use Safety and effectiveness in pediatric patients below the age of 10 years have not been established.

Pregnancy Category B Reproduction studies have been performed in the mouse, rat, rabbit, and monkey, via various routes of administration, at doses 10 times or more the topical human dose and have revealed no significant evidence of impaired fertility or harm to the fetus due to ciclopirox. There are, however, no adequate or well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

HOW SUPPLIED Ciclopirox Topical Suspension USP, 0.77% is supplied in 30 mL (NDC 51672-1323-3) and 60 mL (NDC 51672-1323-4) bottles. Bottle space provided to allow for vigorous shaking before each use. Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

General Ciclopirox Topical Suspension USP is not for ophthalmic use. Keep out of reach of children.

PRECAUTIONS If a reaction suggesting sensitivity or chemical irritation should occur with the use of Ciclopirox Topical Suspension USP, treatment should be discontinued and appropriate therapy instituted. Information for Patients The patient should be told to: Use the medication for the full treatment time even though signs/symptoms may have improved and notify the physician if there is no improvement after four weeks. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing) indicative of possible sensitization. Avoid the use of occlusive wrappings or dressings. Carcinogenesis, Mutagenesis, Impairment of Fertility A carcinogenicity study in female mice dosed cutaneously twice per week for 50 weeks followed by a 6-month drug-free observation period prior to necropsy revealed no evidence of tumors at the application site. The following in vitro and in vivo genotoxicity tests have been conducted with ciclopirox olamine: studies to evaluate gene mutation in the Ames Salmonella /Mammalian Microsome Assay (negative) and Yeast Saccharomyces Cerevisiae Assay (negative) and studies to evaluate chromosome aberrations in vivo in the Mouse Dominant Lethal Assay and in the Mouse Micronucleus Assay at 500 mg/kg (negative). The following battery of in vitro genotoxicity tests were conducted with ciclopirox: a chromosome aberration assay in V79 Chinese Hamster Cells, with and without metabolic activation (positive); a gene mutation assay in the HGPRT – test with V79 Chinese Hamster Cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA Synthesis Assay in A549 Human Cells (negative)). An in vitro Cell Transformation Assay in BALB/C3T3 Cells was negative for cell transformation. In an in vivo Chinese Hamster Bone Marrow Cytogenetic Assay, ciclopirox was negative for chromosome aberrations at 5000 mg/kg. Pregnancy Category B Reproduction studies have been performed in the mouse, rat, rabbit, and monkey, via various routes of administration, at doses 10 times or more the topical human dose and have revealed no significant evidence of impaired fertility or harm to the fetus due to ciclopirox. There are, however, no adequate or well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Caution should be exercised when Ciclopirox Topical Suspension USP, 0.77% is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients below the age of 10 years have not been established.