LOPROX Shampoo Ref.[10861] Active ingredients: Ciclopirox olamine

The pharmacodynamics of LOPROX Shampoo are unknown.

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.

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.

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/2/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 5,000 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).

In two randomized, double-blind clinical trials, subjects 16 years and older with seborrheic dermatitis of the scalp applied LOPROX Shampoo or its vehicle twice weekly for 4 weeks. Subjects who were immunocompromised, those with psoriasis or atopic dermatitis, women of childbearing potential not using adequate contraception, and pregnant or lactating women were excluded from the clinical trials. An evaluation of the overall status of the seborrheic dermatitis, the presence and severity of erythema or inflammation, and scaling was made at Week 4, using a scale of 0=none, 1=slight, 2=mild, 3=moderate, 4=pronounced, and 5=severe. Effective treatment was defined as achieving a score of 0 (or a score of 1 if the baseline score was ≥3) simultaneously for status of the seborrheic dermatitis, erythema or inflammation, and scaling at Week 4. Ciclopirox shampoo was shown to be statistically significantly more effective than vehicle in both trials. Efficacy results for the two trials are presented in Table 1 below.

Table 1. Effective Treatment Rates at Week 4 in Trials 1 and 2:

Efficacy for African American subjects was not demonstrated, although only 53 African American subjects were enrolled in the two pivotal trials.