calcipotriene

1 INDICATIONS AND USAGE Calcipotriene foam is indicated for the topical treatment of plaque psoriasis of the scalp and body in adults and pediatric patients 4 years of age and older. Calcipotriene foam, is a vitamin D analog indicated for the topical treatment of plaque psoriasis of the scalp and body in adults and pediatric patients 4 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Calcipotriene foam is for topical use only. Calcipotriene foam is not for oral, ophthalmic, or intravaginal use. Apply a thin layer of calcipotriene foam twice daily to the affected areas and rub in gently and completely. Avoid contact with the face and eyes. For topical use only; not for oral, ophthalmic, or intravaginal use. ( 2 ) Apply twice daily. ( 2 )

5 WARNINGS AND PRECAUTIONS Flammability: Contents are flammable. Instruct the patient the avoid fire, flame, and smoking during and immediately following application. ( 5.1 ) Effects on Calcium Metabolism: If elevation of serum calcium occurs, instruct patients to discontinue treatment until normal calcium levels are restored. ( 5.2 ) 5.1 Flammability The propellant in calcipotriene foam is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. 5.2 Effects on Calcium Metabolism Elevation of serum calcium has occurred with use of calcipotriene. If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored.

4 CONTRAINDICATIONS Calcipotriene foam should not be used by patients with known hypercalcemia. Do not use in patients with known hypercalcemia. ( 4 )

8.1 Pregnancy Risk Summary Although there are no available data on the drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes in pregnant women exposed to calcipotriene foam, systemic exposure to calcipotriene is likely to be low [see Clinical Pharmacology (12.2 , 12.3) ] . In animal reproduction studies, oral administration of calcipotriene to pregnant rats and rabbits during the period of organogenesis resulted in an increased incidence of minor skeletal abnormalities, including enlarged fontanelles and extra ribs in rats and an increased incidence of minor skeletal abnormalities, including incomplete ossification of pubic bones and forelimb phalanges in rabbits (see Data ) . The available data do not allow the calculation of relevant comparisons between the systemic exposure of calcipotriene observed in animal studies to the systemic exposure that would be expected in humans after topical use of calcipotriene foam. 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.

6 ADVERSE REACTIONS Adverse reactions reported in ≥ 1% of subjects treated with Calcipotriene foam and at a higher incidence than subjects treated with vehicle were application site erythema and application site pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . ( 6 ) 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Calcipotriene foam was studied in four vehicle-controlled trials. A total of 1094 adult subjects with plaque psoriasis, including 654 exposed to calcipotriene foam, were treated twice daily for 8 weeks. Adverse reactions reported in ≥1% of subjects treated with calcipotriene foam and at a higher incidence than subjects treated with vehicle were application 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