Calcipotriene

WARNINGS Avoid contact with the eyes or mucous membranes. Discontinue use if a sensitivity reaction occurs or if excessive irritation develops on uninvolved skin areas. Drug product is flammable. Keep away from open flame.

PRECAUTIONS General Use of Calcipotriene Topical Solution, 0.005% (Scalp Solution), may cause transient irritation of both lesions and surrounding uninvolved skin. If irritation develops, Calcipotriene Topical Solution, 0.005% (Scalp Solution), should be discontinued. For external use only. Keep out of the reach of children. Always wash hands thoroughly after use. Reversible elevation of serum calcium has occurred with use of topical calcipotriene. If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored. Information for Patients Patients using Calcipotriene Topical Solution, 0.005% (Scalp Solution) should receive the following information and instructions: This medication is to be used only as directed by the physician. It is for external use only. Avoid contact with the face or eyes. As with any topical medication, patients should wash their hands after application. This medication should not be used for any disorder other than that for which it was prescribed. Patients should report to their physician any signs of adverse reactions. Patients that apply Calcipotriene Topical Solution, 0.005% (Scalp Solution) to exposed portions of the body should avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.) Carcinogenesis, Mutagenesis, Impairment of Fertility When calcipotriene was applied topically to mice for up to 24 months at dosages of 3, 10 and 30 μg/kg/day (corresponding to 9, 30 and 90 μg/m 2 /day), no significant changes in tumor incidence were observed when compared to control. In a study in which albino hairless mice were exposed to both UVR and topically applied calcipotriene, a reduction in the time required for UVR to induce the formation of skin tumors was observed (statistically significant in males only), suggesting that calcipotriene may enhance the effect of UVR to induce skin tumors. Patients that apply Calcipotriene Topical Solution, 0.005% (Scalp Solution) to exposed portions of the body should avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.). Physicians may wish to limit or avoid use of phototherapy in patients that use Calcipotriene Topical Solution, 0.005% (Scalp Solution). Calcipotriene did not elicit any mutagenic effects in an Ames mutagenicity assay, a mouse lymphoma TK locus assay, a human lymphocyte chromosome aberration assay, or in a micronucleus assay conducted in mice. Studies in rats at doses up to 54 μg/kg/day (324 μg/m 2 /day) of calcipotriene indicated no impairment of fertility or general reproductive performance. Pregnancy Teratogenic Effects: Pregnancy Category C Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40-60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 μg/kg/day (132 μg/m 2 /day). Rabbits administered 36 μg/kg/day (396 μg/m 2 /day) resulted in fetuses with a significant increase in the incidences of pubic bones, forelimb phalanges, and incomplete bone ossification. In a rat study, oral doses of 54 μg/kg/day (318 μg/m 2 /day) resulted in a significantly higher incidence of skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. The enlarged fontanelles are most likely due to calcipotriene’s effect upon calcium metabolism. The maternal and fetal calculated no-effect exposures in the rat (43.2 μg/m 2 /day) and rabbit (17.6 μg/m 2 /day) studies are greater than the expected human systemic exposure level (0.13 μg/m 2 /day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, Calcipotriene Topical Solution, 0.005% (Scalp Solution), should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers There is evidence that maternal 1,25-dihydroxy vitamin D 3 (calcitriol) may enter the fetal circulation, but it is not known whether it is excreted in human milk. The systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring vitamin. Because many drugs are excreted in human milk, caution should be exercised when Calcipotriene Topical Solution, 0.005% (Scalp Solution) is administered to a nursing woman. Pediatric Use Safety and effectiveness of Calcipotriene Topical Solution, 0.005% (Scalp Solution), in pediatric patients have not been specifically established. Because of a higher ratio of skin surface area to body mass, pediatric patients are at greater risk than adults of systemic adverse effects when they are treated with topical medication. Geriatric Use Of the total number of patients in clinical studies of calcipotriene solution, approximately 16% were 65 or older, while approximately 4% were 75 and over. The results of an analysis of severity of skin-related adverse events showed no differences for subjects over 65 years compared to those under 65 years, but greater sensitivity of some older individuals cannot be ruled out.

ADVERSE REACTIONS In controlled clinical trials, the most frequent adverse reactions reported to be related to Calcipotriene Topical Solution, 0.005% (Scalp Solution), use were transient burning, stinging and tingling, which occurred in approximately 23% of patients. Rash was reported in about 11% of patients. Dry skin, irritation and worsening of psoriasis were reported in 1-5% of patients. Skin atrophy, hyperpigmentation, hypercalcemia, and folliculitis were not observed in these studies, but cannot be excluded. To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .