ciclopirox

1 INDICATIONS AND USAGE Ciclopirox Shampoo, 1% is indicated for the topical treatment of seborrheic dermatitis of the scalp in adults. • Ciclopirox Shampoo, 1% is an antifungal indicated for the topical treatment of seborrheic dermatitis of the scalp in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Ciclopirox Shampoo, 1% is not for ophthalmic, oral, or intravaginal use. Wet hair and apply approximately 1 teaspoon (5 mL) of Ciclopirox Shampoo, 1% to the scalp. Up to 2 teaspoons (10 mL) may be used for long hair. Lather and leave on hair and scalp for 3 minutes. A timer may be used. Avoid contact with eyes. Rinse off. Treatment should be repeated twice per week for 4 weeks, with a minimum of 3 days between applications. If a patient with seborrheic dermatitis shows no clinical improvement after 4 weeks of treatment with Ciclopirox Shampoo, 1%, the diagnosis should be reviewed. • Apply approximately 1 teaspoon of Ciclopirox Shampoo, 1% to the scalp twice per week for 4 weeks. ( 2 ) • For topical use only. Not for ophthalmic, oral, or intravaginal use. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Ciclopirox Shampoo 1% is a shampoo containing 1% ciclopirox. Each gram (equivalent to 0.96 mL) of Ciclopirox Shampoo 1% contains 10 mg ciclopirox, USP in a colorless and translucent shampoo base. Shampoo, 1% ( 3 )

4 CONTRAINDICATIONS None. None ( 4 )

6 ADVERSE REACTIONS The most frequently reported adverse reactions are pruritus, burning, and erythema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151, and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 CLINICAL TRIALS EXPERIENCE Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In 626 subjects treated with ciclopirox shampoo twice weekly in the two pivotal clinical trials, the most frequent adverse events were increased itching in 1% of subjects, and application site reactions, such as burning, erythema, and itching, also in 1 % of subjects. 6.2 POSTMARKETING EXPERIENCE The following adverse reactions have been identified during post approval use of ciclopirox shampoo: hair discoloration and abnormal hair texture, alopecia, irritation and rash. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratogenic Effects: Pregnancy Category B There are no adequate or well-controlled studies in pregnant women. Therefore, Ciclopirox Shampoo, 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Oral embryofetal developmental studies were conducted in mice, rats, rabbits and monkeys. Ciclopirox or ciclopirox olamine was orally administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 77, 125, 80 and 38.5 mg/kg/day ciclopirox in mice, rats, rabbits and monkeys, respectively (approximately 13, 42, 54 and 26 times the maximum recommended human dose based on body surface area comparisons, respectively). Dermal embryofetal developmental studies were conducted in rats and rabbits with ciclopirox olamine dissolved in PEG 400. Ciclopirox olamine was topically administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 92 mg/kg/day and 77 mg/kg/day ciclopirox in rats and rabbits, respectively (approximately 31 and 54 times the maximum recommended human dose based on body surface area comparisons, respectively). 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Ciclopirox Shampoo, 1% is administered to a nursing woman. 8.4 Pediatric Use No clinical trials have been conducted in subjects younger than 16 years. 8.5 Geriatric Use In clinical trials, the safety and tolerability of ciclopirox shampoo, 1% in the population 65 years and older was comparable to that of younger subjects. Results of the efficacy analysis in those subjects 65 years and older showed effectiveness in 25 of 85 (29%) subjects treated with ciclopirox shampoo, 1%, and in 15 of 61 (25%) subjects treated with the vehicle; due to the small sample size, a statistically significant difference was not demonstrated. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity to adverse effects in some older individuals cannot be ruled out.

12.1 Mechanism of Action Ciclopirox is a hydroxypyridone antifungal agent although the relevance of this property for the indication of seborrheic dermatitis is not known. Ciclopirox acts by chelation of polyvalent cations (Fe 3 + or Al 3 +), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

11 DESCRIPTION Ciclopirox Shampoo, 1% contains the synthetic antifungal agent, ciclopirox for topical use. Each gram (equivalent to 0.96 mL) of Ciclopirox Shampoo, 1% contains 10 mg ciclopirox in a shampoo base consisting of disodium laureth sulfosuccinate, laureth-2, purified water, sodium chloride, and sodium laureth sulfate. Ciclopirox Shampoo, 1% is a colorless, translucent solution. The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1 H )-pyridone, with the empirical formula C 12 H 17 NO 2 and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0]. The chemical structure is: chemical structure image

16 HOW SUPPLIED/STORAGE AND HANDLING Ciclopirox Shampoo, 1% is colorless and translucent, and is supplied in 120 mL plastic bottles (NDC 51672-1351-8). Discard unused product after initial treatment duration. Store at 20° - 25°C (68° - 77°F) [see USP Controlled Room Temperature]. Keep out of reach of children.