FOR TOPICAL DERMATOLOGIC USE ONLY.

Not for Ophthalmic, Oral or Intravaginal Use.

Rx Only

Calcipotriene ointment, 0.005% contains the compound calcipotriene, a synthetic vitamin D3 derivative for topical dermatological use.

Chemically, calcipotriene is (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola- 5,7,10(19),22-tetraene-1α,3β,24-triol-, with the empirical formula C27H40O3, a molecular weight of 412.6, and the following structural formula:

Calcipotriene is a white or off-white crystalline substance. Calcipotriene ointment contains calcipotriene 50 μg/g in an ointment base of disodium phosphate dihydrate, edetate disodium, mineral oil, petrolatum, propylene glycol, α-tocopherol, steareth-2 and purified water.

In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin. Calcipotriene is a synthetic analog of vitamin D3.

Clinical studies with radiolabelled ointment indicate that approximately 6% (± 3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (± 2.6%, SD) when applied to normal skin, and much of the absorbed active is converted to inactive metabolites within 24 hours of application.

Vitamin D and its metabolites are transported in the blood, bound to specific plasma proteins. The active form of the vitamin, 1,25-dihyroxy vitamin D3 (calcitriol), is known to be recycled via the liver and excreted in the bile. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound.

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.

Adequate and well-controlled trials of patients treated with calcipotriene ointment have demonstrated improvement usually beginning after two weeks of therapy. This improvement continued in patients using calcipotriene once daily and twice daily. After 8 weeks of once daily calcipotriene, 56.7% of patients showed at least marked improvements (6.4% showed complete clearing). After 8 weeks of twice daily calcipotriene, 70.0% of patients showed at least marked improvement (11.3% showed complete clearing).

Subtracting percentages of patients using placebo (vehicle only) from percentages of patients using calcipotriene who had at least marked improvements after 8 weeks yields 39.9% for once daily and 49.6% for twice daily. This adjustment for placebo effect indicated that what might appear to be differences between once and twice daily use may reflect differences in the studies independent from the frequency of dosing. Although there was a numerical difference in comparison across studies, twice daily dosing has not been shown to be superior in efficacy to once daily dosing.

Over 400 patients have been treated in open label clinical studies of calcipotriene for periods of up to one year. In half of these studies, patients who previously had not responded well to calcipotriene were excluded. The adverse events in these extended studies included skin irritation in approximately 25% of patients and worsening of psoriasis in approximately 10% of patients. In one of these open label studies, half of the patients no longer required calcipotriene by 16 weeks of treatment, because of satisfactory therapeutic results.

Calcipotriene ointment, 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.

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.

In controlled clinical trials, the most frequent adverse reactions reported for calcipotriene were burning, itching and skin irritation, which occurred in approximately 10-15% 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.

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.

Apply a thin layer of calcipotriene ointment once or twice daily and rub in gently and completely.

Calcipotriene ointment, 0.005% is available in:

60 gram aluminum tube NDC (51672-4154-3)

120 gram aluminum tube NDC (51672-4154-4)

Store at controlled room temperature 15°C-25°C (59°F-77°F). Do not freeze.

Manufactured by:

Glenmark Generics Ltd.

Colvale-Bardez, Goa 403 513, India

Distributed by:

Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

November 2011

NDC 51672-4154-4

120 g

Calcipotriene

Ointment 0.005%

FOR TOPICAL DERMATOLOGIC USE ONLY. NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE.

Rx only

Keep this and all medications out of the reach of children.

TARO