Calcitriol

CALCITRIOL- calcitriol ointment
Perrigo New York Inc

P51946-2-carton-image

1 INDICATIONS AND USAGE

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.

2 DOSAGE AND ADMINISTRATION

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.

3 DOSAGE FORMS AND STRENGTHS

Ointment, 3mcg/g. Each gram of Calcitriol Ointment contains 3 micrograms (mcg/g) of calcitriol.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Effects on Calcium Metabolism

In controlled clinical trials hypercalcemia was observed in subjects exposed to Calcitriol Ointment. If aberrations in parameters of calcium metabolism occur, treatment should be discontinued until these parameters have normalized. The effects of Calcitriol Ointment on calcium metabolism following treatment durations greater than 52 weeks have not been evaluated. Increased absorption may occur with occlusive use. Calcitriol Ointment should be used with caution in patients receiving medications know to increase the serum calcium level, such as thiazide diuretics, and in patients receiving calcium supplements or high doses of vitamin D.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in 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 Adverse Events Occurring in at least 1% of Subjects in the Two Pooled Vehicle-Controlled Trials
Calcitriol Ointment (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, however the elevation 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 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 the 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary
Available data from pregnancies that occurred during the clinical development of Calcitriol Ointment and published cases of oral and intravenous calcitriol use in pregnant women have not identified a drug associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes.
In animal reproduction studies, topical administration of calcitriol to pregnant rabbits during the period organogenesis resulted in an increased incidence of fetal deaths, as well as an increased incidence of minor skeletal abnormalities (see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposures of calcitriol observed in animal studies to the systemic exposures that would be expected in humans after topical use of Calcitriol Ointment.
The 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
Embryo-fetal development 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 (3ppm) 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 delayed 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.

8.2 Lactation

Risk Summary
There are no data on the presence of calcitriol in human milk, the effects on the breastfed infant or on milk production after treatment with Calcitriol Ointment. It is not known whether topical administration of calcitriol could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Calcitriol Ointment and any potential adverse effects on the breastfed infant from Calcitriol Ointment or from the underlying maternal conditions.
Clinical Considerations
Advise breastfeeding women not to apply Calcitriol Ointment directly to the nipple and areola to avoid direct infant exposure.

8.4 Pediatric Use

The safety and effectiveness of Calcitriol Ointment have been established in pediatric patients age 2 years and older for topical treatment of mild to moderate plaque psoriasis. Use of Calcitriol Ointment in this age group is supported by two adequate and well-controlled 8-week trials and an open label trial in adult subjects, and additional data from trials conducted in pediatric subjects 2 to 17 years of age including:

  • a vehicle controlled 8-week trial in 19 subjects 2 to 12 years of age with mild to moderate plaque psoriasis
  • an open-label 8-week safety and pharmacokinetics (PK) trial in 25 subjects 12 to 17 years of age
  • an open-label 14-day safety and PK trial in 18 subjects 2 to 17 years of age.
  • an open-label 26-week safety and PK trial in 54 subjects 2 to 17 years of age.

Data from 63 subjects ages 2 to 12 years, and 42 subjects ages 13 to 17 years showed no significant effects on indices of calcium metabolism. The systemic exposure of calcitriol in the pediatric subjects was generally comparable to the endogenous levels observed at baseline. No new safety signals were identified in subjects 2 to 17 years [see Clinical Studies (14), Clinical Pharmacology (12.3) and Adverse Reactions (6.1)].
The safety and effectiveness of Calcitriol Ointment in pediatric subjects below the age of 2 years has not been established.

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