CLASSES
Topical Antipsoriasis Agents
DESCRIPTION
Topical vitamin D3 analog
Used for topical symptomatic treatment of chronic plaque psoriasis
Similar receptor binding affinity as natural vitamin D3
COMMON BRAND NAMES
Calcitrene, Dovonex, Dovonex Scalp, Sorilux, Trionex
HOW SUPPLIED
Calcipotriene/Calcitrene/Dovonex Topical Ointment: 0.005%
Calcipotriene/Dovonex Scalp Topical Sol: 0.005%
Calcipotriene/Dovonex/Trionex Topical Cream: 0.005%
Calcipotriene/Sorilux Topical Foam: 0.005%
DOSAGE & INDICATIONS
For the treatment of plaque psoriasis.
NOTE: According to the American Academy of Dermatology (AAD), combining calcipotriene with a topical corticosteroid is more effective than either treatment alone. In addition, fewer adverse events were reported with combination therapy in most clinical studies.
For the treatment of chronic, moderate scalp psoriasis.
Topical dose (scalp solution)
Adults
Apply topically to the affected area(s) of scalp twice daily.
Topical dosage (ointment)
Adults
Apply topically as a thin layer to affected area(s) once daily in the morning or twice daily in the morning and evening for up to 8 weeks. Do not exceed 100 g/week.
Children and Adolescents 2 years and older†
Limited data suggest twice daily application of calcipotriene for up to 8 weeks is effective and well tolerated at dosages up to 50 g/week. Clinical trials including children ages 2 to 14 years demonstrated marked improvement or clearing of psoriasis in more than 60% of patients after twice daily application for up to 8 weeks. The most commonly reported adverse effect was local skin irritation.
Topical dosage (cream)
Adults
Apply topically as a thin layer to affected area(s) twice daily in the morning and evening for up to 8 weeks. Do not exceed 100 g/week.
Topical dosage (foam)
Adults
Apply a thin layer twice daily to the affected areas; rub in gently and completely.
Children and Adolescents 4 years and older
Apply a thin layer twice daily to the affected areas; rub in gently and completely.
MAXIMUM DOSAGE
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.
DOSING CONSIDERATIONS
Hepatic Impairment
No dosage adjustment required.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
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.
STORAGE
Calcitrene :
- Do not freeze
- Store between 59 to 77 degrees F
Dovonex:
- Do not freeze
- Store between 59 to 77 degrees F
Dovonex Scalp:
- Do not freeze
- Flammable, keep away from heat and flame
- Protect from direct sunlight
- Store at controlled room temperature (between 68 and 77 degrees F)
Sorilux:
- Avoid direct heat and sunlight
- Do not freeze
- Do not refrigerate
- Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
- Flammable, keep away from heat and flame
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store upright
Trionex:
- Avoid excessive heat (above 104 degrees F)
- Keep away from heat and flame
- Protect from freezing
- Store at 20 to 25 degrees C (68 to 77 degrees F); excursions permitted between 15 to 30 degrees C (59 to 86 degrees F) USP Controlled Room Temperature
- Store at controlled room temperature (between 68 and 77 degrees F)
CONTRAINDICATIONS / PRECAUTIONS
General Information
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.
Hypercalcemia, hypercalciuria, hypervitaminosis D, nephrolithiasis, occlusive dressing
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.
Accidental exposure, ocular exposure
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.
Children, infants, neonates
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.
Sunlight (UV) exposure
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.
Pregnancy
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.
Breast-feeding
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.
Tobacco smoking
The propellant in calcipotriene topical foam is flammable. Instruct patients to avoid fire, flame, and tobacco smoking during and immediately following application.
ADVERSE REACTIONS
Severe
exfoliative dermatitis / Delayed / 1.0-10.0
skin atrophy / Delayed / 0-1.0
Moderate
erythema / Early / 1.0-10.0
contact dermatitis / Delayed / Incidence not known
hypertension / Early / Incidence not known
constipation / Delayed / Incidence not known
hypercalciuria / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known
depression / Delayed / Incidence not known
Mild
skin irritation / Early / 10.0-15.0
rash / Early / 0-11.0
pruritus / Rapid / 1.0-10.0
xerosis / Delayed / 1.0-10.0
folliculitis / Delayed / 0-1.0
skin hyperpigmentation / Delayed / 0-1.0
weight loss / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
nausea / Early / Incidence not known
anorexia / Delayed / Incidence not known
fatigue / Early / Incidence not known
weakness / Early / Incidence not known
polydipsia / Early / Incidence not known
vomiting / Early / Incidence not known
DRUG INTERACTIONS
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; Risedronate: (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).
Folic Acid, Vitamin B9: (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.
PREGNANCY AND LACTATION
Pregnancy
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.
MECHANISM OF ACTION
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.
PHARMACOKINETICS
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
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.[23819] 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.