Calcipotriene

DESCRIPTION Calcipotriene Ointment USP, 0.005% contains the compound calcipotriene, USP a synthetic vitamin D 3 derivative for topical dermatological use. Chemically, Calcipotriene, USP is 24-cyclopropyl-(1α,3β,5Z,7E,22E,24S)-9,10-Secochola-5,7,10(19),22-tetraene-1,3,24-trioI; with the empirical formula C 27 H 40 O 3 , a molecular weight of 412.62, and the following structural formula: Calcipotriene, USP is a white or almost white crystalline powder. Calcipotriene Ointment USP, 0.005% contains calcipotriene, USP 50 mcg/g in an ointment base of disodium phosphate dihydrate, edetate disodium, mineral oil, white petrolatum, propylene glycol, dl-alpha-tocopherol , steareth-2 and purified water. structure

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

CONTRAINDICATIONS Calcipotriene 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 should not be used on the face.

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

ADVERSE REACTIONS Clinical Trials Experience In controlled clinical trials, the most frequent adverse reactions reported for calcipotriene were burning, itching and skin irritation, which occurred in approximately 10 to 15% of patients. Erythema, dry skin, peeling, rash, dermatitis, worsening of psoriasis including development of facial/scalp psoriasis were reported in 1 to 10% of patients. Other experiences reported in less than 1% of patients included skin atrophy, hyperpigmentation, hypercalcemia, and folliculitis. Once daily dosing has not been shown to be superior in safety to twice daily dosing. Postmarketing Experience The following adverse reactions have been identified during post approval use of Dovonex Ointment. 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. Renal and urinary disorders: hypercalciuria Skin and subcutaneous tissue disorders: application site edema, application site pain, contact dermatitis (including allergic contact dermatitis), depigmentation, hypopigmentation, photosensitivity, rash (including erythematous, maculo-papular, and pustular), and urticaria.

Pregnancy Teratogenic Effects Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40 to 60% of the administered dose. In rabbits, increased maternal and fetal toxicity were noted at a dosage 12 mcg/kg/day (132 mcg/m 2 /day); a dosage of 36 mcg/kg/day (396 mcg/m 2 /day) resulted in a significant increase in the incidence of incomplete ossification of the pubic bones and forelimb phalanges of fetuses. In a rat study, a dosage of 54 mcg/kg/day (318 mcg/m 2 /day) resulted in a significantly increased incidence of skeletal abnormalities (enlarged fontanelles and extra ribs). The enlarged fontanelles are most likely due to calcipotriene’s effect upon calcium metabolism. The estimated maternal and fetal no-effect exposure levels in the rat (43.2 mcg/m 2 /day) and rabbit (17.6 mcg/m 2 /day) studies are approximately equal to the expected human systemic exposure level (18.5 mcg/m 2 /day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, calcipotriene ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pediatric Use Safety and effectiveness of calcipotriene in pediatric patients have not been 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.

OVERDOSAGE Topically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of calcipotriene ointment USP, 0.005%.