Calcipotriene Cream, and Transparent Dressing

Indicated for the treatment of plaque psoriasis.

INDICATIONS AND USAGE Calcipotriene cream, 0.005%, is indicated for the treatment of plaque psoriasis. The safety and effectiveness of topical calcipotriene in dermatoses other than psoriasis have not been established.

Do not use if known hypersensitivity to any of the listed ingredients of any of the components included on the kit.

CONTRAINDICATIONS Calcipotriene cream is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. It should not be used by patients with demonstrated hypercalcemia or evidence of vitamin D toxicity. Calcipotriene cream should not be used on the face.

FOR EXTERNAL USE ONLY. Avoid contact with eyes, lips or mucous membranes.

WARNINGS Contact dermatitis, including allergic contact dermatitis, has been observed with the use of calcipotriene cream.

Stop use and ask a doctor if redness or irritation develops. Keep this and all other medications out of the reach of children. If swallowed, get medical help or contact a Poison Control Center right away. PREGNANCY If pregnant or breast feeding, ask a health professional before use.

PRECAUTIONS General Use of calcipotriene cream may cause transient irritation of both lesions and surrounding uninvolved skin. If irritation develops, calcipotriene cream 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 cream should receive the following information and instructions: 1.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. 2.This medication should not be used for any disorder other than that for which it was prescribed. 3.Patients should report to their physician any signs of adverse reactions. 4.Patients that apply calcipotriene cream 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 mcg/kg/day (corresponding to 9, 30 and 90 mcg/m2/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 cream 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 cream. 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 mcg/kg/day (324 mcg/m2/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 to 60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m2/day). Rabbits administered 36 mcg/kg/day (396 mcg/m2/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 mcg/kg/day (318 mcg/m2/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 mcg/m2/day) and rabbit (17.6 mcg/m2/day) studies are approximately equal to the expected human systemic exposure level (18.5 mcg/m2/day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, calcipotriene cream 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 D3 (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 cream is administered to a nursing woman. Pediatric Use There is evidence that maternal 1,25-dihydroxy vitamin D3 (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 cream is administered to a nursing woman. Geriatric Use Of the total number of patients in clinical studies of calcipotriene cream, approximately 15% were 65 or older, while approximately 3% were 75 and over. There were no significant differences in adverse events for subjects over 65 years compared to those under 65 years of age. However, the greater sensitivity of older individuals cannot be ruled out.

Clinical Trials Experience In controlled clinical trials, the most frequent adverse experiences reported for calcipotriene cream, 0.005% were cases of skin irritation, which occurred in approximately 10 to 15% of patients. Rash, pruritus, dermatitis and worsening of psoriasis were reported in 1 to 10% of patients. Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions associated with the use of calcipotriene cream have been identified post-approval: contact dermatitis, including allergic contact dermatitis.

Teratogenic Effects: Pregnancy Category C Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40 to 60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m2/day). Rabbits administered 36 mcg/kg/day (396 mcg/m2/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 mcg/kg/day (318 mcg/m2/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 mcg/m2/day) and rabbit (17.6 mcg/m2/day) studies are approximately equal to the expected human systemic exposure level (18.5 mcg/m2/day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, calcipotriene cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There is evidence that maternal 1,25-dihydroxy vitamin D3 (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 cream is administered to a nursing woman.

There is evidence that maternal 1,25-dihydroxy vitamin D3 (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 cream is administered to a nursing woman.

Of the total number of patients in clinical studies of calcipotriene cream, approximately 15% were 65 or older, while approximately 3% were 75 and over. There were no significant differences in adverse events for subjects over 65 years compared to those under 65 years of age. However, the greater sensitivity of older individuals cannot be ruled out.