1 INDICATIONS AND USAGE VECTICAL Ointment is a vitamin D analog indicated for the topical treatment of mild to moderate plaque psoriasis in adults 18 years and older. 1.1 Indication VECTICAL Ointment is indicated for the topical treatment of mild to moderate plaque psoriasis in adults 18 years and older. 1.2 Limitations of Use VECTICAL Ointment should not be applied to the eyes, lips, or facial skin.
3 DOSAGE FORMS AND STRENGTHS Each gram of ointment contains 3 micrograms (mcg/g) of calcitriol. Each gram of ointment contains 3 micrograms of calcitriol.
4 CONTRAINDICATIONS None None (4)
5 Warnings and Precautions 5.1 Effects on Calcium Metabolism If aberrations in parameters of calcium metabolism are noted discontinue VECTICAL Ointment until these normalize. (5.1) Avoid excessive exposure of VECTICAL Ointment treated areas to either natural or artificial sunlight. (5.2) In controlled clinical trails with VECTICAL Ointment, 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. However, the increases in calcium and albumin-adjusted calcium levels were less than 10% above the upper limit of normal. If aberrations in parameters of calcium metabolism occur, treatment should be discontinued until these parameters have normalized. The effects of VECTICAL Ointment on calcium metabolism following treatment durations greater than 52 weeks have not been evaluated. Increased absorption may occur with occlusive use. 5.2 Ultraviolet Light Exposure Animal data suggest that the vehicle of VECTICAL Ointment may enhance the ability of ultraviolet radiation (UVR) to induce skin tumors. [see Carcinogenesis, Mutagenesis, Impairment of Fertility (13.1)] Subjects who apply VECTICAL Ointment to exposed skin should avoid excessive exposure of the treated areas to either natural or artificial sunlight, including tanning booths and sun lamps. Physicians may wish to limit or avoid use of phototherapy in patients who use VECTICAL Ointment. 5.3 Unevaluated Uses The safety and effectiveness of VECTICAL Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated. The safety and effectiveness of VECTICAL Ointment in patients with erythrodermic, exfoliative, or pustular psoriasis have not been evaluated.
6 ADVERSE REACTIONS 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. Most common adverse reactions (incidence ≥3%) were lab test abnormality, urine abnormality, psoriasis, hypercalciuria, and pruritus. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact: Galderma Laboratories, L.P. at 866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience VECTICAL Ointment was studied in two vehicle-controlled studies (419 subjects), and in one open label study (324 subjects). The table below describes exposure to VECTICAL Ointment in 743 subjects, including 239 exposed for 6 months and 116 exposed for one year. Four hundred and nineteen subjects were treated with VECTICAL Ointment twice daily for 8 weeks. The population included subjects ages 13 to 87, males (284) and females (135), Caucasians (372) and non-Caucasians (47); with mild (105) to moderate (313) chronic plaque psoriasis. 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, however the elevations were less than 10% above the upper limit of normal [see WARNINGS AND PRECAUTIONS (5.1)] The open label study enrolled 324 subjects with psoriasis who were then treated for up to 52 weeks. Adverse events reported at a rate of greater than or equal to 3% of subjects treated with VECTICAL Ointment were lab test abnormality (8%), urine abnormality (4%), psoriasis (4%), hypercalciuria (3%), and pruritus (3%). Kidney stones were reported in 3 subjects and confirmed in two. 6-1-table 6.2 Postmarketing Experience The following adverse reactions have been identified during world-wide post-approval use of VECTICAL Ointment: acute blistering dermatitis, erythema, pruritus, skin burning sensation, and skin discomfort. 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.
7 DRUG INTERACTIONS VECTICAL Ointment should be used with caution in patients receiving medications known to increase the serum calcium level, such as thiazide diuretics. Caution should also be exercised in patients receiving calcium supplements or high doses of vitamin D [see WARNINGS AND PRECAUTIONS (5.1)].
8 USE IN SPECIFIC POPULATION 8.1 Pregnancy Teratogenic Effects: Pregnancy Category C. VECTICAL Ointment contains calcitriol which has been shown to be fetotoxic. There are no adequate and well-controlled studies for VECTICAL Ointment in pregnant women. VECTICAL Ointment should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus. Teratogenicity studies with calcitriol were performed in which rats were treated orally at dosages up to 0.9 mcg/kg/day (5.4 mcg/m2/day) and in which rabbits received topical application of calcitriol ointment (3 ppm) to 6.4% of the body surface area. No effects on reproductive or fetal parameters were observed in rats. In rabbits, topically applied calcitriol induced a significantly elevated mean post-implantation loss and an increased incidence of minor skeletal abnormalities due to retarded ossification of the pubic bones. A slightly increased incidence of skeletal variation (extra 13th rib, reduced ossification of epiphyses) was also observed. These effects may have been secondary to maternal toxicity. Based on the recommended human dose and instructions for use, it is not possible to calculate human dose equivalents for animal exposures in these studies. 8.3 Nursing Mothers It is not known whether calcitriol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VECTICAL Ointment is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of VECTICAL Ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported experience has not identified differences in responses between the elderly and younger patients.