Dovonex

Browse PDR's full list of drug information

Dovonex

Classes

Topical Antipsoriasis Agents

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.

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

Common Brand Names

Calcitrene, Calsodore, Dovonex, Dovonex Scalp, Sorilux, Trionex

Dea Class

Rx

Description

Topical vitamin D3 analog
Used for topical symptomatic treatment of chronic plaque psoriasis
Similar receptor binding affinity as natural vitamin D3

Dosage And Indications
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.

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.

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; 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.

How Supplied

Calcipotriene/Calcitrene/Dovonex Topical Ointment: 0.005%
Calcipotriene/Calsodore/Dovonex/Trionex Topical Cream: 0.005%
Calcipotriene/Dovonex Scalp Topical Sol: 0.005%
Calcipotriene/Sorilux Topical Foam: 0.005%

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.

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.

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.