Ciclopirox

CICLOPIROX- ciclopirox shampoo
Teligent Pharma, Inc.

structural formulaPDP — carton

1 INDICATION AND USAGE

Ciclopirox Shampoo is indicated for the topical treatment of seborrheic dermatitis of the scalp in adults.

2 DOSAGE AND ADMINISTRATION

Ciclopirox Shampoo is not for ophthalmic, oral, or intravaginal use.

Wet hair and apply approximately 1 teaspoon (5 mL) of LOPROX Shampoo 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, the diagnosis should be reviewed.

3 DOSAGE FORMS AND STRENGTHS

Ciclopirox is a shampoo containing 1% ciclopirox.

Each gram (equivalent to 0.96 mL) of Ciclopirox Shampoo contains 10 mg ciclopirox in a colorless and translucent shampoo base.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Local Effects

If a reaction suggesting sensitivity or irritation occurs with the use of Ciclopirox Shampoo, treatment should be discontinued and appropriate therapy instituted.

Contact of Ciclopirox Shampoo with the eyes should be avoided. If contact occurs, rinse thoroughly with water.

In patients with lighter hair color, hair discoloration has been reported.

6 ADVERSE REACTIONS

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 Post Marketing 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 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 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 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, 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.

11 DESCRIPTION

Ciclopirox Shampoo 1% contains the synthetic antifungal agent, ciclopirox for topical use.

Each gram (equivalent to 0.96 mL) of Ciclopirox Shampoo 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 is a colorless, translucent solution. The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone, with the empirical formula C12 H17 NO2 and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0]. The chemical structure is:

structural formula
(click image for full-size original)

12 CLINICAL PHARMACOLOGY

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 (Fe3+ or Al3+), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

12.2 Pharmacodynamics

The pharmacodynamics of Ciclopirox Shampoo are unknown.

12.3 Pharmacokinetics

In a study in patients with seborrheic dermatitis of the scalp, application of 5 mL ciclopirox shampoo 1% twice weekly for 4 weeks, with an exposure time of 3 minutes per application, resulted in detectable serum concentrations of ciclopirox in 6 out of 18 patients. The serum concentrations measured throughout the dosing interval on Days 1 and 29 ranged from 10.3 ng/mL to 13.2 ng/mL. Total urinary excretion of ciclopirox was less than 0.5% of the administered dose.

12.4 Microbiology

Ciclopirox is fungicidal in vitro against Malassezia furfur (Pityrosporum spp.), P. ovale , and P. orbiculare.

The clinical significance of antifungal activity in the treatment of seborrheic dermatitis is not known.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

A 104-week dermal carcinogenicity study in mice was conducted with ciclopirox cream applied at doses up to 1.93% (100 mg/kg/day or 300 mg/m2 /day). No increase in drug related neoplasms was noted when compared to control.

The following in vitro genotoxicity tests have been conducted with ciclopirox: evaluation of gene mutation in the Ames Salmonella and E. coli assays (negative); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells, with and without metabolic activation (positive); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells in the presence of supplemental Fe3+ , with and without metabolic activation (negative); gene mutation assays in the HGPRT-test with V79 Chinese hamster lung fibroblast 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/c 3T3 cells was negative for cell transformation. In an in vivo Chinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at a dosage of 5000 mg/kg body weight.

A combined oral fertility and embryofetal developmental study was conducted in rats with ciclopirox olamine. No effect on fertility or reproductive performance was noted at the highest dose tested of 3.85 mg/kg/day ciclopirox (approximately 1.3 times the maximum recommended human dose based on body surface area comparisons).

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