Calcipotriene is a vitamin D3 analog indicated for the topical symptomatic treatment of chronic plaque psoriasis. Calcipotriene is structurally similar to naturally occurring calcitriol. In 1986, vitamin D analogs were discovered to be effective in the treatment of psoriasis, however, oral vitamin D has limited usefulness due to side effects associated with the large dosages often needed for therapy. Hence, topical calcipotriene provides a safe and effective alternative to oral vitamin D. Marked improvement in clearing of psoriatic lesions occurs in approximately 50% to 70% of patients, although lesions can recur within 2 to 3 months following discontinuance of treatment. Clinical trials comparing calcipotriene with other antipsoriatic agents demonstrated that calcipotriene is at least as effective as betamethasone and is superior to short-contact anthralin.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Calcipotriene is for external use only. Do not apply to the face or eyes.
-Wash hands after use.
Cream/Ointment/Lotion Formulations
-Cream or Ointment: Apply a thin film to the affected area and rub into the skin gently and completely.
-Cream with Transparent Dressing: Apply a thin film to the affected area and rub into the skin gently and completely. Once rubbed in completely, apply transparent dressing to the affected area as needed as a protectant.
Other Topical Formulations
-Scalp Solution: Comb hair to remove scaly debris, and after suitably parting apply scalp solution. Rub in gently and completely, taking care to prevent the solution spreading onto the forehead. Avoid application of solution to eyes or unaffected scalp margins.
-Topical Foam: Shake well; dispense a small amount of foam into palm of the hand and gently rub into the affected area until foam disappears. If not treating the hands, wash after use. Avoid contact with face, eyes, mouth, and vagina. The propellant in the topical foam is flammable. Instruct the patient to avoid fire, flame, and/or smoking during and immediately following application.
Compared to control, no significant change in the incidence of tumor formation was reported when calcipotriene was applied topically to mice for up to 24 months at dosages of 3, 10, and 30 mcg/kg/day; however, a study conducted in albino hairless mice demonstrated that exposure to UV radiation along with application of topical calcipotriene shortened the time to formation of skin tumors. This finding suggests that calcipotriene may increase the effect of UV radiation on skin tumor formation. Patients should be advised to avoid excessive exposure to natural or artificial sunlight while on calcipotriene. It may also be prudent to limit or avoid the use of phototherapy in patients using calcipotriene.
Skin irritation has been reported in with the topical use of calcipotriene (10% to 15% with the ointment and cream and 23% with the solution), and has included itching, stinging, tingling, and burning sensations. Rash has been reported in up to 11% of patients. Erythema, application site pain, xerosis, pruritus, worsening of psoriasis (including the development of facial or scalp psoriasis), peeling, and exfoliative dermatitis occur in 1% to 10% of patients and may require discontinuation of treatment. In rare instances, allergic contact dermatitis has also been reported. Skin reactions often resolve with continued use. Facial dermatitis occurred in up to 10% of patients in early trials during therapy with calcipotriene. This adverse reaction seemed related to direct application of the product to the face and, as a result, calcipotriene ointment is not recommended for application to the face. Resolution of symptoms occurs within days of treatment withdrawal.
Hypercalcemia and hypercalciuria occur almost exclusively when the recommended 100 grams per week dosage is approached or exceeded. Although calcium and bone metabolism in humans appear to be unaffected during short-term therapy of stable plaque psoriasis when calcipotriene is used in recommended dosages (less than 100 grams per week), a significant increase in urine calcium was seen when calcipotriene was administered at the maximum weekly dosage (100 grams per week) for 4 weeks. The urine calcium of subjects receiving less than 77 grams per week for 1 year was unchanged. The clinical significance of these findings remains undetermined; however, the investigators caution against using calcipotriene in patients with hypercalcemia or those predisposed to renal stone formation. In general, the effectiveness and safety from long-term use are similar to short-term use. Symptoms of severe hypercalcemia include abdominal pain, constipation, depression, fatigue, hypertension, anorexia, weight loss, muscle weakness, nausea, vomiting, and thirst (polydipsia).
Adverse reactions reported in less than 1% of patients during therapy with calcipotriene included skin atrophy, skin hyperpigmentation, and folliculitis. During postmarketing use of the topical foam, cases of application site vesicles have been reported. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Calcipotriene should not be used in patients with a history of hypersensitivity reactions to the drug or any components used in the preparation of the commercial product.
Calcipotriene is contraindicated when hypercalcemia or hypervitaminosis D are evident. Although systemic absorption of this agent is minimal, hypercalcemia, hypervitaminosis D, and/or hypercalciuria may occur. Hypercalcemia and/or hypercalciuria may increase renal calculi formation in patients with a history of nephrolithiasis. Topical application of more than 100 g/week should be avoided since hypercalcemia is more likely when this dose is exceeded. Do not cover with an occlusive dressing as this may enhance absorption of calcipotriene. Monitoring serum and urine calcium does not appear necessary during treatment at recommended dosages.
Calcipotriene should not be applied to the face; avoid ocular exposure. Accidental exposure to unaffected areas of skin or scalp margins may lead to skin irritation and should be avoided. Calcipotriene should be discontinued if irritation develops. In some instances skin irritation has resolved with continued use.
Safety and efficacy of calcipotriene cream, ointment, and scalp solution have not been established in pediatric patients (i.e. neonates, infants, children, or adolescents) younger than 18 years. Safety and efficacy of calcipotriene foam have not been established in pediatric patients younger than 4 years. Age-related differences in treating psoriasis may result in increased sensitivity to calcipotriene. Children are at a greater risk of developing systemic adverse effects to topical medications because of a higher ratio of skin surface area to body mass.
Excessive exposure to natural or artificial sunlight (UV) exposure with topical application of calcipotriene may increase the risk of skin tumor formation and should be avoided. It may also be prudent to limit or avoid the use of phototherapy or other photosensitizing agents.
There are no human data to associate the use of calcipotriene during pregnancy with an increased risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, oral administration of calcipotriene to pregnant rats and rabbits during organogenesis resulted in an increased incidence of minor skeletal abnormalities (e.g., enlarged fontanelles, extra ribs, incomplete ossification of pubic bones and forelimb phalanges). Systemic absorption following application of the calcipotriene foam to humans was below the limit of quantification (10 pg/mL). The expected systemic exposure level in humans following topical application of calcipotriene ointment is 18.5 mcg/m2/day, which is approximately equal to the maternal and fetal calculated no-effects exposures seen in rats and rabbits, 43.2 mcg/m2/day and 17.6 mcg/m2/day, respectively. Calcipotriene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
According to the manufacturer, it is not known whether calcipotriene is excreted into human milk. After topical administration, only small amounts of the drug are absorbed into systemic circulation. Calcipotriene is a synthetic derivative of calcitriol, an active form of vitamin D. The American Academy of Pediatrics (AAP) considers vitamin D usually compatible with breast-feeding. Therefore, it is unlikely that topical administration of calcipotriene would pose significant risk to a nursing infant. Ensure that the infant does not come in contact in the areas where calcipotriene has been applied. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The propellant in calcipotriene topical foam is flammable. Instruct patients to avoid fire, flame, and tobacco smoking during and immediately following application.
For the treatment of plaque psoriasis:
Topical dosage (ointment):
Adults: Apply a thin layer topically to the affected skin area(s) once or twice daily. Max: 100 g/week/m2. Guidelines recommend long-term use of topical vitamin D analogues (up to 52 weeks) for the treatment of mild to moderate psoriasis. Use of combination treatments with vitamin D analogues and potent class 2 and 3 topical corticosteroids up to 52 weeks is recommended for the treatment of psoriasis. Topical calcipotriene combined with hydrocortisone for 8 weeks can be used for the treatment of facial psoriasis. Calcipotriene plus betamethasone dipropionate gel is recommended for 4 to 12 weeks for the treatment of mild to moderate scalp psoriasis. May consider the use of topical vitamin D analogues twice daily on weekdays with high-potency topical corticosteroids twice daily on weekends or application of morning high-potency topical corticosteroids and evening topical vitamin D analogues for the treatment of psoriasis. The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis. The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis; it may lead to lower cumulative doses of methotrexate and increased time to relapse after methotrexate discontinuation.
Children and Adolescents 2 to 17 years*: Apply a thin layer topically to the affected skin area(s) twice daily. Adult Max: 100 g/week/m2. Guidelines recommend calcipotriene for childhood plaque psoriasis. Rotational therapy with topical vitamin D analogues, topical calcineurin inhibitors, emollients, tar-based therapies, and topical corticosteroids may be considered in children as steroid-sparing regimens that may reduce potential adverse effects from over reliance on topical steroid therapy.
Topical dosage (cream):
Adults: Apply a thin layer topically to the affected skin area(s) twice daily. Safety and efficacy have been demonstrated in persons treated for 8 weeks. Max: 100 g/week/m2. Guidelines recommend long-term use of topical vitamin D analogues (up to 52 weeks) for the treatment of mild to moderate psoriasis. Use of combination treatments with vitamin D analogues and potent class 2 and 3 topical corticosteroids up to 52 weeks is recommended for the treatment of psoriasis. Topical calcipotriene combined with hydrocortisone for 8 weeks can be used for the treatment of facial psoriasis. Calcipotriene plus betamethasone dipropionate gel is recommended for 4 to 12 weeks for the treatment of mild to moderate scalp psoriasis. May consider the use of topical vitamin D analogues twice daily on weekdays with high-potency topical corticosteroids twice daily on weekends or application of morning high-potency topical corticosteroids and evening topical vitamin D analogues for the treatment of psoriasis. The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis. The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis; it may lead to lower cumulative doses of methotrexate and increased time to relapse after methotrexate discontinuation.
Topical dosage (foam):
Adults: Apply a thin layer topically to the affected skin area(s) twice daily. Max: 100 g/week/m2. Guidelines recommend long-term use of topical vitamin D analogues (up to 52 weeks) for the treatment of mild to moderate psoriasis. Use of combination treatments with vitamin D analogues and potent class 2 and 3 topical corticosteroids up to 52 weeks is recommended for the treatment of psoriasis. Topical calcipotriene combined with hydrocortisone for 8 weeks can be used for the treatment of facial psoriasis. Calcipotriene foam is recommended for 4 to 12 weeks for the treatment of mild to moderate scalp psoriasis. May consider the use of topical vitamin D analogues twice daily on weekdays with high-potency topical corticosteroids twice daily on weekends or application of morning high-potency topical corticosteroids and evening topical vitamin D analogues for the treatment of psoriasis. The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis. The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis; it may lead to lower cumulative doses of methotrexate and increased time to relapse after methotrexate discontinuation.
Children and Adolescents 4 to 17 years: Apply a thin layer topically to the affected skin area(s) twice daily. Adult Max: 100 g/week/m2. Guidelines recommend calcipotriene for childhood plaque psoriasis. Rotational therapy with topical vitamin D analogues, topical calcineurin inhibitors, emollients, tar-based therapies, and topical corticosteroids may be considered in children as steroid-sparing regimens that may reduce potential adverse effects from over reliance on topical steroid therapy.
Topical dosage (scalp solution):
Adults: Apply topically to the psoriatic scalp area(s) twice daily. Max: 100 g/week/m2. Guidelines recommend long-term use of topical vitamin D analogues (up to 52 weeks) for the treatment of mild to moderate psoriasis. Use of combination treatments with vitamin D analogues and potent class 2 and 3 topical corticosteroids up to 52 weeks is recommended for the treatment of psoriasis. Calcipotriene plus betamethasone dipropionate gel is recommended for 4 to 12 weeks for the treatment of mild to moderate scalp psoriasis. May consider the use of topical vitamin D analogues twice daily on weekdays with high-potency topical corticosteroids twice daily on weekends or application of morning high-potency topical corticosteroids and evening topical vitamin D analogues for the treatment of psoriasis. The addition of calcipotriene to standard dose acitretin is recommended for the treatment of moderate to severe psoriasis. The addition of topical calcipotriene to standard dose methotrexate therapy is recommended for the treatment of moderate to severe psoriasis; it may lead to lower cumulative doses of methotrexate and increased time to relapse after methotrexate discontinuation.
Maximum Dosage Limits:
-Adults
100 g/week topically for the cream and lotion; specific maximum dosage information not available for foam or scalp solution.
-Geriatric
100 g/week topically for the cream and lotion; specific maximum dosage information not available for foam or scalp solution.
-Adolescents
Specific maximum dosage information not available for foam; safety and efficacy have not been established for the cream, lotion, or scalp solution.
-Children
4 to 12 years: Specific maximum dosage information not available for foam; safety and efficacy have not been established for the cream, lotion, or scalp solution.
1 to 3 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment required.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Calcium Acetate: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Carbonate: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Carbonate; Magnesium Hydroxide: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Carbonate; Simethicone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Chloride: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium Gluconate: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcium; Vitamin D: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Chromium: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Polycarbophil: (Moderate) Use calcipotriene cautiously with other agents that can produce hypercalcemia, including calcium polycarbophil. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use.
Porfimer: (Major) Avoid the concomitant use of porfimer with calcipotriene. Calcipotriene may enhance the ability of ultraviolet radiation to induce skin tumors. Coadministration of photosensitizing agents such as porfimer may increase this risk.
Pyridoxine, Vitamin B6: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Verteporfin: (Major) Use caution if coadministration of verteporfin with calcipotriene is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like calcipotriene may increase the risk of a photosensitivity reaction.
The mechanism of action of calcipotriene, a synthetic analog of vitamin D3, is similar to naturally occurring 1,25-(OH)2-D3 (calcitriol). Calcitriol (i.e., active vitamin D3) is the metabolite of cholecalciferol (i.e., inactive vitamin D3). Calcipotriene binds to vitamin D receptors on epidermal cells and tissue cells. Activation of this ligand-receptor complex results in inhibition of cell proliferation and induction of cell differentiation in psoriatic skin. In addition, calcipotriene binds to vitamin D receptors on lymphocytes. Calcipotriene is also similar to calcitriol in its ability to suppress thymocyte proliferation, T-helper function, and lymphocyte proliferation. The exact role of these immunologic mechanisms in the reduction of psoriatic lesions is unknown.
The binding affinity of calcipotriene to intestinal calcitriol receptors is similar to that of calcitriol, however animal studies demonstrated that calcipotriene is 100-200 times less potent than calcitriol on calcium metabolism when given systemically. It has been suggested that rapid liver metabolism or extensive metabolism of calcipotriene in epidermal keratinocytes is responsible for this difference.
During short-term therapy of stable plaque psoriasis, calcium and bone metabolism in humans appear to be unaffected when calcipotriene is used at the recommended dosage (<100 grams/week). Calcipotriene administered for 4 weeks at the maximum weekly dosage (100 grams/week) resulted in significant increases in urine calcium.
Calcipotriene is administered topically. Although the distribution of absorbed calcipotriene and its metabolites have not been described, it is presumed to be similar to other vitamin D derivatives. It is unknown if calcipotriene and its metabolites cross the placenta or are distributed into breast milk. Absorbed calcipotriene is rapidly and extensively converted in the liver to a 24-ketone and a 22,23-hydrogenated derivative. In vitro data have shown that the parent compound is also metabolized by human keratinocytes. All metabolites identified thus far have negligible activity compared with the parent compound. Calcipotriene is minimally excreted in the urine and feces (less than 1%).
Affected cytochrome P450 isoenzymes: None
-Route-Specific Pharmacokinetics
Topical Route
Approximately 6% of a topical dose of calcipotriene is systemically absorbed when applied to psoriatic skin. Clinical improvement of psoriatic lesions occurs within 2 weeks, with maximal benefits observed in 4 to 8 weeks. The drug demonstrates a dose-dependent effect on erythema, thickness, and scaling of lesions. In a study evaluating the systemic absorption of calcipotriene ointment (n = 16) and foam (n = 16) applied to a body surface area of 5% to 10% in psoriasis patients, plasma concentration were measurable (below 25 pg/mL) in 5 of 16 patients treated with calcipotriene ointment compared to undetectable (less than 10 pg/mL) in 15 of 16 patients treated with calcipotriene foam.
-Special Populations
Pediatrics
Systemic concentrations of calcipotriene were below the limits of quantification (i.e., 10 pg/mL) after topical application of the 0.005% foam for 15 days to pediatric patients (ages 12 to 17 years) with plaque psoriasis affecting a mean body surface area (excluding face and scalp) of 24% and scalp of 43%. Similarly, another study involving 11 pediatric patients (ages 7 to 11 years) with plaque psoriasis affecting a mean body surface area of 10% failed to detect quantifiable systemic drug concentrations (10 pg/mL) in any patient who received twice daily administration of the topical foam for 2 weeks.