Calcipotriene

Calcipotriene is a prescription medicine used on the skin to treat plaque psoriasis in adults. This medication is a synthetic form of vitamin D.

Administration

Topical Administration

Apply topically to the skin as a 0.005% cream or as a fixed-combination ointment containing calcipotriene 0.005% and betamethasone dipropionate 0.064% (equivalent to 0.05% of betamethasone);2 5 apply to the scalp as a 0.005% solution or as a fixed-combination suspension containing calcipotriene 0.005% and betamethasone dipropionate 0.064% (equivalent to 0.05% of betamethasone).3 6

For dermatologic use only; not intended for oral, ophthalmic, or intravaginal use.2 3 5 6 Avoid contact with face, eyes, axillae, groin, and other mucous membranes.2 3 5 6

Apply cream in a thin film and rub gently and completely into affected area.2

Apply calcipotriene and betamethasone dipropionate fixed-combination ointment and rub gently and completely into affected area.5

For scalp psoriasis, comb hair to remove scaly debris; part the hair and apply calcipotriene solution to affected area; rub gently and completely into scalp.3 4 Avoid contact with forehead or uninvolved scalp margins.3

For scalp psoriasis, apply calcipotriene and betamethasone dipropionate fixed-combination suspension to affected areas; part the hair before applying the suspension.6 Shake bottle prior to each use.6

Wash hands thoroughly after application process.2 3 5 6

Dosage

Adults

Apply 0.005% cream sparingly to affected area twice daily.2

Apply ointment containing calcipotriene 0.005% and betamethasone 0.05% to the affected area(s) once daily.5

Apply 0.005% scalp solution to affected area twice daily.3

Apply suspension containing calcipotriene 0.005% and betamethasone 0.05% to affected area(s) of the scalp once daily for 2 weeks or until cleared.6

Prescribing Limits

Adults

Use of 0.005% cream >8 weeks not evaluated.2

Maximum 100 g weekly of the fixed-combination calcipotriene 0.005% and betamethasone 0.05% ointment.5 Do not apply to >30% of body surface area.5 Do not exceed 4 consecutive weeks of therapy.5

Use of 0.005% scalp solution >8 weeks not evaluated.3

Maximum 100 g weekly of the fixed-combination calcipotriene 0.005% and betamethasone 0.05% suspension.6 Do not exceed 8 consecutive weeks of therapy.6

Special Populations

No special population dosage recommendations at this time.2 3 5 6

No formal drug interaction studies to date.2 3 5 6

Absorption

Bioavailability

Topically applied ointment and scalp solution can be absorbed through normal intact skin;2 3 absorption may increase when applied to psoriasis plaques.2 Systemic absorption of calcipotriene cream not evaluated.2

Following topical application of ointment to psoriasis plaques or normal skin, about 6% or 5%, respectively, of the drug reaches systemic circulation.2

Following topical application of scalp solution to normal skin or psoriatic plaques on the scalp, <1% of the drug reaches systemic circulation.3

Distribution

Extent

Topical calcipotriene may cross the placenta; not known if distributed into milk.2 3 5 6

Elimination

Metabolism

Rapidly metabolized by the liver to inactive metabolites.2 3 5 6

Elimination Route

Excreted principally in bile.2 3

Storage

Topical

15–25°C; do not freeze.2

Fixed-combination calcipotriene-betamethasone dipropionate ointment: 20–25°C (may be exposed to 15–30°C).5

15–25°C; do not freeze.3 Avoid sunlight.3

Fixed-combination calcipotriene-betamethasone dipropionate suspension: 20–25°C (may be exposed to 15–30°C).6 Do not refrigerate.6 Store bottle in outer carton when not in use and use within 3 months after opening.6

Avoid contact with the eyes or mucous membranes. Discontinue use if a sensitivity reaction occurs or if excessive irritation develops on uninvolved skin areas.

Drug product is flammable. Keep away from open flame.

PRECAUTIONS

General

Use of  Calcipotriene Topical Solution, 0.005% (Scalp Solution) may cause transient irritation of both lesions and surrounding uninvolved skin. If irritation develops, Calcipotriene Topical Solution, 0.005% (Scalp Solution) should be discontinued.

For external use only. Keep out of the reach of children. Always wash hands thoroughly after use.

Reversible elevation of serum calcium has occurred with use of topical Calcipotriene. If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored.

Information for Patients

Patients using Calcipotriene Topical Solution, 0.005% (Scalp Solution) should receive the following information and instructions:

1. This medication is to be used only as directed by the physician. It is for external use only. Avoid contact with the face or eyes. As with any topical medication, patients should wash their hands after application.
2. This medication should not be used for any disorder other than that for which it was prescribed.
3. Patients should report to their physician any signs of adverse reactions.
4. Patients that apply Calcipotriene Topical Solution, 0.005% (Scalp Solution) to exposed portions of the body should avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.).

Carcinogenesis, Mutagenesis, Impairment of Fertility

When Calcipotriene was applied topically to mice for up to 24 months at dosages of 3, 10 and 30 µg/kg/day (corresponding to 9, 30 and 90 µg/m2/day), no significant changes in tumor incidence were observed when compared to control.  In a study in which albino hairless mice were exposed to both UVR and topically applied Calcipotriene, a reduction in the time required for UVR to induce the formation of skin tumors was observed (statistically significant in males only), suggesting that Calcipotriene may enhance the effect of UVR to induce skin tumors. Patients that apply Calcipotriene Topical Solution, 0.005% (Scalp Solution) to exposed portions of the body should avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.). Physicians may wish to limit or avoid use of phototherapy in patients that use Calcipotriene Topical Solution, 0.005% (Scalp Solution).

Calcipotriene did not elicit any mutagenic effects in an Ames mutagenicity assay, a mouse lymphoma TK locus assay, a human lymphocyte chromosome aberration assay, or in a micronucleus assay conducted in mice.

Studies in rats at doses up to 54 µg/kg/day (324 µg/m2/day) of Calcipotriene indicated no impairment of fertility or general reproductive performance.

Pregnancy

Teratogenic Effects: Pregnancy Category C

Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40-60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 µg/kg/day (132 µg/m2/day). Rabbits administered 36 µg/kg/day (396 µg/m2/day) resulted in fetuses with a significant increase in the incidences of pubic bones, forelimb phalanges, and incomplete bone ossification. In a rat study, oral doses of 54 µg/kg/day (318 µg/m2/day) resulted in a significantly higher incidence of skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. The enlarged fontanelles are most likely due to Calcipotriene’s effect upon calcium metabolism. The maternal and fetal calculated no-effect exposures in the rat (43.2 µg/m2/day) and rabbit (17.6 µg/m2/day) studies are greater than the expected human systemic exposure level (0.13 µg/m2/day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, Calcipotriene Topical Solution, 0.005% (Scalp Solution), should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

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. Because many drugs are excreted in human milk, caution should be exercised when Calcipotriene Topical Solution, 0.005% (Scalp Solution) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of  Calcipotriene Topical Solution, 0.005% (Scalp Solution) in pediatric patients have not been specifically 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.

Geriatric Use

Of the total number of patients in clinical studies of Calcipotriene solution, approximately 16% were 65 or older, while approximately 4% were 75 and over. The results of an analysis of severity of skin-related adverse events showed no differences for subjects over 65 years compared to those under 65 years, but greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity to calcipotriene or any component of the formulation; patients with demonstrated hypercalcemia or evidence of vitamin D toxicity; use on the face (cream, ointment); patients with acute psoriatic eruptions (scalp solution)

Documentation of allergenic cross-reactivity for Vitamin D derivatives is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

There are no dosage adjustments provided in the manufacturer’s labeling.

For external use only. Avoid contact with face and eyes (rinse thoroughly with water if contact occurs).

Cream, foam, ointment: Apply to affected skin; rub in gently and completely. Wash hands thoroughly after use.

Foam, solution (scalp psoriasis): Prior to using, comb hair to remove debris; apply only to scalp lesions. Rub in gently and completely. Wash hands thoroughly after use. Foam should be applied when hair is dry.

If the use of multiple topical agents is necessary, apply the various agents at separate times throughout the day (Menter 2009).

Administration advice:
-Avoid contact with the face or eyes.
-Always wash hands thoroughly after use.

Storage requirements:
-Do not freeze
-Solution: Avoid sunlight
-Foam: Flammable: Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120 F (49 C)

Patient advice:
-Patients that apply this drug to exposed portions of the body should avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.).