on site erythema (2%) and application site pain (3%). the incidence of these adverse reactions was similar between the body and scalp. in an open-label study, 19 pediatric subjects age 12 to less than 17 years applied calcipotriene foam twice daily for 14 days and once on day 15. adverse reactions included application site pain, application site pruritus and pruritus [see clinical pharmacology ( 12.2 and 12.3 ) and pediatric use ( 8.4 )] .] in an open-label study, 36 pediatric subjects age 4 to less than 12 years applied calcipotriene foam twice daily for up to 8 weeks. adverse reactions included application site pain and contact dermatitis [see clinical pharmacology ( 12.2 and 12.3 ) and pediatric use ( 8.4 )] . 6.2 postmarketing experience the following adverse reactions have been identified during post approval use of calcipotriene foam. 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. skin and subcutaneous: application site vesicles

am. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data embryofetal development studies were conducted with calcipotriene after oral administration in rats and rabbits. pregnant rats received daily oral administration of calcipotriene during the period of organogenesis. fetuses from dams dosed with 54 mcg/kg/day (318 mcg/m 2 /day) exhibited a significantly increased incidence of minor skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. the enlarged fontanelles are most likely due to calcipotriene's effect upon calcium metabolism. there were no effects on the incidence of major malformations in fetuses. pregnant rabbits received daily oral administration of calcipotriene during the period of organogenesis. increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m 2 /day). fetuses from does dosed with 36 mcg/kg/day (396 mcg/m 2 /day) exhibited a significantly increased incidence of minor skeletal abnormalities including incomplete ossification of pubic bones and forelimb phalanges. there were no effects on the incidence of major malformations in fetuses. 8.2 lactation risk summary there are no data on the presence of topically administered calcipotriene in human or animal milk, the effects on the breastfed infant, or the effects on milk production. after topical administration of calcipotriene foam, concentrations of calcipotriene in plasma are low, and therefore, concentrations in human milk are likely to be low [see clinical pharmacology ( 12.3 )] . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for and any potential adverse effects on the breastfed child from calcipotriene foam or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of calcipotriene foam have been established in pediatric patients age 4 years and older for topical treatment of plaque psoriasis of the scalp and body. use of calcipotriene foam in this age group is supported by two adequate and well controlled 8-week trials in adults and adolescents 12 years of age and older, with additional data from a 15-day open-label safety and pharmacokinetics (pk) study conducted in 19 subjects 12 to less than 17 years of age; and an 8-week open-label safety and pk study in 36 subjects 4 to 11 years of age with psoriasis. data from 19 subjects aged 12 to less than 17 years and 18 subjects aged 5 to 11 years showed no significant effects on indices of calcium metabolism. systemic concentrations of calcipotriene were not quantifiable in the two studies in subjects aged 7 years to less than 17 years. [see clinical studies ( 14 ), clinical pharmacology ( 12.2 , 12.3 ) and adverse reactions ( 6.1 )] . the safety and effectiveness of calcipotriene foam in pediatric patients less than 4 years of age have not been established. 8.5 geriatric use clinical trials of calcipotriene foam did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients.

isk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data embryofetal development studies were conducted with calcipotriene after oral administration in rats and rabbits. pregnant rats received daily oral administration of calcipotriene during the period of organogenesis. fetuses from dams dosed with 54 mcg/kg/day (318 mcg/m 2 /day) exhibited a significantly increased incidence of minor skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. the enlarged fontanelles are most likely due to calcipotriene's effect upon calcium metabolism. there were no effects on the incidence of major malformations in fetuses. pregnant rabbits received daily oral administration of calcipotriene during the period of organogenesis. increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m 2 /day). fetuses from does dosed with 36 mcg/kg/day (396 mcg/m 2 /day) exhibited a significantly increased incidence of minor skeletal abnormalities including incomplete ossification of pubic bones and forelimb phalanges. there were no effects on the incidence of major malformations in fetuses.

ectiveness of calcipotriene foam in pediatric patients less than 4 years of age have not been established.

%-36.5%). there was no relationship between urinary calcium/creatinine ratio (comparing week 2 to baseline) and % bsa treated. 12.3 pharmacokinetics the systemic absorption of calcipotriene in subjects with psoriasis of the body was evaluated at steady state following application of either calcipotriene foam or calcipotriene ointment to a body surface area of 5% to 10%. in the calcipotriene foam treatment group, 15 out of 16 subjects had calcipotriene plasma concentrations below the limit of quantitation (10 pg/ml), while in the calcipotriene ointment treated group, 5 out of 16 subjects had measurable calcipotriene plasma concentrations at various time points. all measurable plasma calcipotriene concentrations were below 25 pg/ml. the pharmacokinetics of calcipotriene foam, 0.005% was investigated when applied topically for 15 days to 17 subjects aged 12 to less than 17 years with moderate plaque psoriasis involving a mean bsa of 24%, excluding face and scalp, and a mean scalp involvement of 43%. systemic concentration of calcipotriene were not quantifiable in any of the subjects (limit of quantification = 10 pg/ml). in 11 pediatric subjects 7 to 11 years of age with plaque psoriasis involving a mean bsa of 10%, plasma concentration of calcipotriene was measured following 2 weeks of twice daily administration of calcipotriene foam. no subject had quantifiable calcipotriene plasma concentration (limit of quantification = 10 pg/ml). the systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring vitamin d. absorbed calcipotriene is known to be converted to inactive metabolites within 24 hours of application and the metabolism occurs via a similar pathway to the natural hormone.

pg/ml). in 11 pediatric subjects 7 to 11 years of age with plaque psoriasis involving a mean bsa of 10%, plasma concentration of calcipotriene was measured following 2 weeks of twice daily administration of calcipotriene foam. no subject had quantifiable calcipotriene plasma concentration (limit of quantification = 10 pg/ml). the systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring vitamin d. absorbed calcipotriene is known to be converted to inactive metabolites within 24 hours of application and the metabolism occurs via a similar pathway to the natural hormone.

g defined as a score of "clear" (grade 0) or "almost clear" (grade 1) and at least 2 grade improvement from the baseline score. approximately 30% of enrolled subjects were graded as "mild" on the isga scale. the study population ranged in age from 12 to 89 years with 10 subjects less than 18 years of age at baseline. the subjects were 54% male and 88% caucasian. table 2 presents the efficacy results for each trial. table 2. number and percent of subjects achieving success for body at week 8 in each trial trial 1 trial 2 calcipotriene foam n = 223 vehicle foam n = 113 calcipotriene foam n = 214 vehicle foam n = 109 number (%) of subjects with treatment success 31 (14%) 8 (7%) 58 (27%) 17 (16%) in one trial, subjects graded as "mild" at baseline showed a greater response to vehicle than calcipotriene foam. table 3 presents the success rates by disease severity at baseline for each trial. table 3. number and percent of subjects achieving success for body by baseline isga score and by trial isga scores at baseline trial 1 trial 2 calcipotriene foam (n = 223) vehicle foam (n = 113) calcipotriene foam (n = 214) vehicle foam (n = 109) mild 2/73 (2.7%) 3/34 (8.8%) 8/56 (14.3%) 4/31 (12.9%) moderate 29/150 (19.3%) 5/79 (6.3%) 50/158 (31.6%) 13/78 (16.7%) in another multi-center, randomized, double-blind, vehicle-controlled clinical trial, a total of 363 subjects with moderate plaque psoriasis of the scalp and body were randomized 1:1 to calcipotriene foam or vehicle. subjects applied the assigned treatment to the affected areas twice daily for 8 weeks. baseline disease severity of the scalp was graded using a 6-point isga; a score of "moderate" corresponded to grade 3. the primary efficacy evaluation for scalp involvement was carried out at week 8 with treatment success being defined as a score of "clear" (grade 0) or "almost clear" (grade 1). the study population ranged in age from 12 to 97 years with 11 subjects less than 18 years of age at baseline. the subjects were 60% male and 87% caucasian. table 4 presents the efficacy results for the trial. table 4. number and percent of subjects achieving success for scalp at week 8 trial 3 calcipotriene foam n = 181 vehicle foam n = 182 number (%) of subjects with treatment success 74 (41%) 44 (24%) the contribution to efficacy of individual components of the vehicle has not been established.