CALCITROL

Calcitriol (calcitriol) Ointment 3 mcg/g is a vitamin D analog intended for topical application to the skin. The chemical name of the active ingredient is (5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-1α,3β,25-triol. The structural formula is: Calcitriol is a white or almost white crystalline solid. It is practically insoluble in water, soluble in alcohol and in fatty oils. The molecular formula is C 27 H 44 O 3 , and the molecular weight is 416.64. Calcitriol Ointment is a translucent ointment containing 3 mcg/g (0.0003% w/w) of calcitriol, packaged in aluminum tubes with screw caps. Other components of the ointment are mineral oil, dl-α-tocopherol, and white petrolatum.

Calcitrol Ointment is a vitamin D analog indicated for the topical treatment of mild to moderate plaque psoriasis in adult and pediatric patients 2 years and older. ( 1.1 ) Limitations of Use The safety and effectiveness of Calcitriol Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated. ( 1.2 ) 1.1 Indication Calcitriol Ointment is indicated for the topical treatment of mild to moderate plaque psoriasis in adults and pediatric patients 2 years and older. 1.2 Limitations of Use The safety and effectiveness of Calcitriol Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated.

Apply Calcitriol Ointment to affected areas twice daily, morning and evening Adults: • The maximum weekly dose should not exceed 200 grams. Pediatrics: • 2 to 6 years of age: the maximum weekly dose should not exceed 100 grams • 7 years of age and older: the maximum weekly dose should not exceed 200 grams Calcitriol Ointment should not be applied to the eyes, lips, or facial skin. Calcitriol Ointment is for topical use only. Calcitriol Ointment is not for oral, ophthalmic or intravaginal use. Apply Calcitriol Ointment to affected areas of the body twice daily. ( 2 ) Adults: • The maximum weekly dose should not exceed 200 grams. ( 2 ) Pediatrics: • 2 to 6 years of age: the maximum weekly dose should not exceed 100 grams. ( 2 ) • 7 years of age and older: the maximum weekly dose should not exceed 200 grams. ( 2 ) For topical use only. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

None None ( 4 )

Most common adverse reactions (incidence ≥ 3%) are hypercalcemia, hypercalciuria, and skin discomfort. ( 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. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Calcitriol Ointment was studied in two vehicle-controlled trials and one open label trial, resulting in 743 subjects exposed to Calcitriol Ointment. Table 1 describes adverse events in subjects treated with Calcitriol Ointment twice daily for 8 weeks. The population included subjects ages 13 to 87 years, males (284) and females (135), Caucasians (372) and non-Caucasians (47); with mild (105) to moderate (313) chronic plaque psoriasis. Table 1. Selected Averse Events Occurring in at least 1% of Subjects in the Two Pooled Vehicle-Controlled Trials Calcitriol (n = 419) Vehicle Ointment (n = 420) Discomfort skin 3% 2% Pruritus 1% 1% Among subjects having laboratory monitoring, hypercalcemia was observed in 24% (18/74) of subjects exposed to active drug and in 16% (13/79) of subjects exposed to vehicle, the elevations were less than 10% above the upper limit of normal ) [see Warnings and Precautions ( 5.1 ) ]. The open label trial enrolled 324 subjects with psoriasis who were treated for up to 52 weeks and included 239 subjects exposed for 6 months and 116 subjects exposed for one year. Adverse events reported at a rate of greater than or equal to 3% of subjects treated with Calcitriol Ointment were lab test abnormality (8%), urine abnormality (4%), psoriasis (4%), hypercalciuria (3%), and discomfort of skin (3%). Kidney stones were reported in 3 subjects and confirmed in two. 6.2 Postmarketing Experience The following adverse reactions have been identified during world-wide post-approval use of Calcitriol Ointment: acute blistering dermatitis, erythema and skin burning sensation. 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.

16.2 Storage Store at Controlled Room temperature 68° - 77°F (20° - 25°C) with excursions permitted between 59° - 86°F (15° - 30°C). [See USP Controlled Room Temperature.] Do not freeze or refrigerate.