Calcipotriene (Topical)



INN:

Calcipotriol {03}

BAN:
Calcipotriol {04}

VA CLASSIFICATION
Primary: DE802

Commonly used brand name(s): Dovonex.

Another commonly used name is
MC 903 {02} {03} {04}.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antipsoriatic (topical)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Psoriasis (treatment)—Calcipotriene cream and ointment are indicated for the treatment of [mild] {05} {21} to moderate plaque psoriasis {01} {02} {05} {06} {07} {08} {21}. [Calcipotriene cream and ointment also may be used in the treatment of extensive or severe chronic plaque psoriasis.{05}{09}{24} However, its use in this type of psoriasis is generally not recommended because of increased risk of hypercalcemia, secondary to excessive absorption of the medication when there is extensive skin involvement. If calcipotriene is to be used for severe extensive psoriasis, it is necessary to monitor the serum and urinary calcium levels at regular intervals.{05}]
—[Calcipotriene ointment is also used in combination with ultraviolet B light (UVB) phototherapy in the treatment of psoriasis.{05}{20}]

Psoriasis, of scalp (treatment)—Calcipotriene topical solution is indicated to treat chronic, moderately severe psoriasis of the scalp {30}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Synthetic vitamin D 3 derivative {01} {05} {20} {21}.
Molecular weight—
    412.6 {01} {03} {04}

Mechanism of action/Effect:

Unknown; {26} however, calcipotriene inhibits keratinocyte proliferation (without any evidence of cytotoxic effect) and induces terminal differentiation of keratinocytes, thus reversing the abnormal keratinocyte change in psoriasis. {02} {05} {16} {20} Calcipotriene exhibits a vitamin D–like effect by competing for the cellular receptors for calcitriol (1,25[OH] 2D 3), a biologically active metabolite of vitamin D. These calcitriol receptors have been identified on keratinocytes of both normal and psoriatic skin {05} {06} {08}. In vitro data suggest that calcipotriene is equal to calcitriol in its ability to inhibit proliferation and induce differentiation of many cell types {30}. Animal data show calcipotriene to be 100 to 200 times less potent in its effects on calcium metabolism as compared with those of calcitriol {30}.

In open studies involving 400 patients treated with topical calcipotriene for up to 1 year, half of the studies excluded patients who had responded poorly to previous use of calcipotriene {01}. Calcipotriene used for 8 weeks resulted in:    • Ointment—With use of calcipotriene once a day, 57% of patients studied showed marked improvement and 6% complete clearing of psoriasis {01}. In another study of patients using ointment twice a day, 70% of patients showed marked improvement and 11% complete clearing of psoriasis {01}. Since these patients were not compared in the same study, the difference, among other factors, may be due to the population studied, the vehicle, and the time of the year when treated. {35} Using calcipotriene twice a day is not considered to be superior in efficacy to its use once a day {01}.
   • Cream (used twice a day)—50% of patients showed marked improvement and 4% showed complete clearing {29} in patients studied.
   • Solution (used twice a day)—17% of patients showed marked improvement and 14% showed complete clearing in 31% of patients studied {30}.



Other actions/effects:

Calcipotriene seems to have an immunoregulatory role that involves the skin immune system, {10} {11} and is associated with variable decreases in keratinocyte expression of markers of activation {10} {11}. Calcipotriene may reduce the release of cytokines from different cell lineages; it may also govern a down-regulation of cell adhesion molecules (CAMs) that are known to mediate the passage of activated T-lymphocytes in the dermis and in the epidermis, thereby producing a reduction of cellular infiltrates in psoriasis {11}.

Absorption:

For the cream—Systemic absorption of the cream has not been studied but is thought to be less than that of the ointment {34}.

For the ointment—Approximately 6% (± 3%, SD) of the applied dose of radiolabeled calcipotriene ointment is absorbed systemically when the ointment is applied topically to psoriasis plaques; about 5% (± 2.6%, SD) is absorbed when applied to normal skin {01}.

For the solution—Approximately 1% of the applied dose is systemically absorbed {34}.

Protein binding:

In vitro, the affinity of calcipotriene for human serum vitamin D–binding protein is 30 times less than that of calcitriol {20}.

Biotransformation:

Clinical studies using radiolabeled calcipotriene ointment have shown that much of the active substance absorbed is converted to inactive metabolites within 24 hours following topical application to psoriasis plaques and normal skin {01}. In animal studies, calcipotriene is rapidly metabolized in the liver following systemic uptake {01} {20} and converted to inactive metabolites identified as MC 1046 and MC 1080 {20}.

Elimination:
    Only small amounts (< 1%) of radiolabeled calcipotriene were recovered in the urine and feces following topical application of this medication in 4 patients with psoriasis {20}.


Precautions to Consider

Carcinogenicity

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of calcipotriene {01}.

Mutagenicity

Calcipotriene did not show any mutagenic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, the human lymphocyte chromosome aberration test, and the mouse micronucleus test {01}.

Pregnancy/Reproduction
Fertility—
Studies in rats given calcipotriene in doses up to 54 mcg per kg of body weight (mcg/kg) per day (318 mcg per square meter of body surface area [mcg/m 2] per day) showed no impairment of fertility or of general reproductive performance {01}.

Pregnancy—
Adequate and well-controlled studies have not been done in humans {01} {05}. There is evidence that calcitriol crosses the placenta; similar distribution is expected for calcipotriene {30}.

Maternal and fetal toxicity increased in pregnant rabbits given oral doses of 12 mcg/kg per day (132 mcg/m 2 per day). Incomplete ossification of the fetal pubic bones and forelimb phalanges occurred at doses of 36 mcg/kg per day (396 mcg/m 2 per day) {01}. Skeletal abnormalities, such as enlarged fontanelles and extra ribs, occurred in the fetuses of pregnant rats given oral doses of 54 mcg/kg per day (318 mcg/m 2 per day). The effect of skeletal enlargement is probably due to the alteration of calcium metabolism by the medication {01}.

The amount of the dose expected to be absorbed systemically from a topical application of calcipotriene is approximately 18.5 mcg/m 2 per day for the ointment (corresponding to about 5 to 6% of the applied dose) {01} {29} and approximately 0.13 mcg/m 2 per day for the scalp solution (corresponding to 1% of the applied dose) {30} {34}.

Following oral administration (absorbed dose corresponds to 40 to 60% of oral dose), adverse fetal development or skeletal teratogenic effects occurred in rats at absorbed doses of approximately 156 mcg/m 2 per day. These effects also occurred in rabbits at absorbed doses of approximately 61 mcg/m 2 and 198 mcg/m 2 per day. No adverse fetal effects were seen at absorbed doses of 43.2 mcg/m 2 per day in rats or 17.6 mcg/m 2 per day in rabbits {01} {34}.

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether calcipotriene is distributed into breast milk. However, problems in humans have not been documented. {01} {05}

Pediatrics

Appropriate studies on the relationship of age to the effects of calcipotriene have not been performed in the pediatric population. Safety and efficacy have not been established {01} {05}. Because of a higher ratio of skin surface area to body mass, children are at greater risk than adults of systemic adverse effects when they are treated with topical medication {01}.

Although the severity of stable psoriasis did not improve in pediatric patients enrolled in one prospective, placebo-controlled, double-blind study, 43 children between 2 and 14 years of age showed less skin redness and scaliness after being treated for 8 weeks with topical calcipotriene. Treatment of less than 30% of total body surface area did not produce any short-term, detectable alterations of bone and calcium metabolism in these children {32}.


Geriatrics


According to the manufacturer, about 12% of the total number of patients in the clinical studies of calcipotriene ointment were 65 years of age or older, while about 4% were 75 years of age and older. Skin-related adverse effects with use of the ointment were more severe in patients over 65 years of age than in those under 65 years of age {01}.


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
» Calcium concentrations, serum    (rapid, transient, and reversible increase may occur, which may or may not be dose-related; {05} {09} {22} if increase in serum calcium is outside the normal range, treatment should be discontinued until normal calcium levels are restored {01} {09})


» Calcium concentrations, urine    (transient, reversible increase may occur, usually with excessive doses; {09} {13} one study showed an increase in urine calcium level when calcipotriene was used within the recommended maximum dose of 100 grams per week; this increase was attributed to the following mechanisms: increased absorption of calcium by the gut, increased mobilization from bone, or altered renal handling; urine calcium levels may rise even in the absence of any apparent change in the serum calcium levels {12})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Psoriasis, of scalp, acute eruptions    (solution should not be applied to acute psoriatic eruptions; medication should be discontinued if skin irritation develops on involved or surrounding uninvolved skin {30})


Risk-benefit should be considered when the following medical problems exist
» Hypercalcemia{01} or
» Hypercalciuria, pre-existing{12} or
» Hypervitaminosis D{01}    (may result in renal impairment due to increased renal calculi formation, secondary to precipitation of calcium salts in the renal parenchyma [nephrocalcinosis] {06} {12})


Hypersensitivity to calcipotriene or to other components of the preparation, history of{01}{05}
» Nephrolithiasis, history of    (may further aggravate condition due to increased renal calculi formation {12})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Calcium concentrations, serum{09}    (transient, reversible increase may occur; generally, treatment with calcipotriene at recommended doses of up to 100 grams per week does not result in changes in laboratory values of serum calcium; however, it is recommended that baseline serum calcium levels be obtained prior to treatment and that monitoring be done at regular intervals, especially if calcipotriene is used at doses in excess of 100 grams per week or if it is used for severe psoriasis with extensive skin involvement; if serum calcium levels become elevated, treatment with calcipotriene should be discontinued and serum calcium levels should be measured once a week until the levels return to normal; patients with marginally elevated serum calcium may be treated with calcipotriene, provided that the serum calcium is monitored at suitable intervals {05})


» Calcium concentrations, urine{09}    (transient, reversible increase may occur; {12} urine calcium is considered a more sensitive indicator of toxicity than is serum calcium; {12} {13} patients with extensive psoriasis who may require a dose approaching 100 grams per week should be screened for hypercalciuria by obtaining baseline urine calcium levels prior to treatment; urine calcium of these patients should be monitored if this dose is continued for more than a few weeks {12})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Dermatitis {01}{02}{17}{18}(redness and swelling of skin with itching)—incidence of 10 to 15% for cream and ointment and 1 to 5% for solution
    
skin rash {01}{02}{21}—incidence of 1 to 10% for cream and ointment and 11% for solution
    
worsening of psoriasis, including development of psoriasis of the face and scalp{01}{19}{21} —incidence of 1 to 10% for cream and ointment and 1 to 5% for solution

Note: The incidence of side/adverse effects may be somewhat underreported since half of the open studies involving 400 patients treated with topical calcipotriene ointment for up to 1 year excluded patients who had responded poorly to previous use of calcipotriene {01}.


Incidence rare—1% or less for ointment, not reported for cream or solution
    
Atrophy of skin {01}(thinning, weakness, or wasting away of skin)
    
folliculitis {01}(burning, itching, and pain in hairy areas; pus in the hair follicles)
    
hypercalcemia, severe {01}{09}{14}{15}(high blood levels of calcium{09}{23}; in severe cases, abdominal pain, constipation, depression, easy fatigability, high blood pressure, loss of appetite, loss of weight, muscle weakness, nausea, thirst, and vomiting{14}{23})—usually asymptomatic in mild cases
    
hypercalciuria (high urine levels of calcium{09}{12}{13})—usually asymptomatic

Note: Hypercalcemia and hypercalciuria are usually reversible upon withdrawal of the medication {09}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning, irritation, or itching of skin, transient{01}{02}{06}{07}{08}{21} —incidence of 20% for cream and ointment and 23% for solution upon application{01}{06}
    
dryness or peeling of skin —incidence of 1 to 10% for cream and ointment and 1 to 5% for solution
    
erythema {01}{02}{06}{21}(redness of skin)—incidence of 1 to 10% for ointment

Incidence rare
    
Hyperpigmentation {01}(darkening of treated skin)—incidence of less than 1% for cream and ointment, not reported with solution





Overdose
For specific information on the agents used in the management of calcipotriene overdose, see:
   • Corticosteroids—Glucocorticoid Effects (Systemic) monograph;
   • Diuretics, Loop (Systemic) monograph; and/or
   • Potassium Supplements (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute effects
    
Hypercalcemia {01} {05} and/or hypercalciuria, severe {12} {13} {09}{14}{23}(abdominal pain, constipation, depression, easy fatigability, high blood pressure, loss of appetite, loss of weight, muscle weakness, nausea, thirst, and vomiting)—less severe cases are usually asymptomatic


Treatment of overdose
To decrease absorption—For both mild and severe cases of hypercalcemia and/or hypercalciuria, treatment with calcipotriene should be discontinued. For mild cases, withdrawal of the medication should be sufficient treatment. {05} {12}

To enhance elimination—For severe hypercalcemia, intensive hydration to increase calcium excretion is necessary. Fluids should be given both orally and parenterally (sodium chloride given intravenously is most effective). {23} {28}

Specific treatment—Diuretics such as furosemide may be given in conjunction with vigorous hydration. Prednisone may also be effective. Sufficient potassium chloride with continuous cardiac monitoring may be given to prevent hypokalemia. For patients with impaired renal function, hemodialysis may be useful. {23} {28}

Monitoring—Fluid intake and output and serum and urine electrolytes should be monitored carefully. {28}

Supportive care—Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Calcipotriene (Topical).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to calcipotriene or to other components of the preparation

Pregnancy—Calcipotriene probably crosses placenta. Human studies have not been done; in animal studies, high oral doses have caused incomplete skeletal development and skeletal abnormalities in fetuses





Use in children—Safety and efficacy have not been established. Children are at greater risk of developing adverse systemic effects than adults when treated with topical medications; however, problems in bone and calcium metabolism did not occur in 43 children between 2 and 14 years of age treated for 8 weeks with topical calcipotriene applied to less than 30% of their body surface areas






Use in the elderly—Skin-related side effects may be more severe when they occur in patients over 65 years of age
Other medical problems, especially acute psoriatic eruptions on the scalp (for topical solution), hypercalcemia, hypercalciuria, hypervitaminosis D, or nephrolithiasis

Proper use of this medication
» For external use only and not for ophthalmic, oral, or intravaginal use; using this medication only as directed by physician {01} {05}

Compliance with full course of therapy

» Not using more than 100 grams of cream or ointment or 60 mL of solution per week {01} {05} {22} or a total dose of more than 5 mg of calcipotriene a week

» Avoiding contact of medication with face, eyes, mucous membranes, or uninvolved skin; washing medication off with water if it accidentally gets onto face, into eyes or mucous membranes, or onto normal skin surrounding the psoriatic area(s) {01} {05}

Applying medication sparingly in folds of skin because of risk of irritation of skin where there is natural occlusion {05} {22} {25}

Washing hands after application to avoid inadvertently transferring medication onto face or uninvolved areas of the skin {01} {05}

Not using medication for any skin disorder other than that for which it was prescribed {01}

For cream and ointment dosage forms
» Applying enough medication to cover affected area(s) of skin and rubbing in gently and completely {05}; avoiding use of occlusive dressing {05} {06} {07}

» When ointment is used in combination with ultraviolet B light (UVB) phototherapy, applying medication after ultraviolet light exposure {05}. This avoids the vehicle's UV-blocking action. Also, UV light can inactivate calcipotriene {31} {36}.

For solution dosage form
Properly preparing scalp before application by combing and removing scaly debris, parting hair for easy access to scalp lesions; applying medication only to visible lesions; rubbing it in gently and completely; not applying on acute psoriatic eruptions

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Medication may cause transient irritation of lesions and surrounding uninvolved skin after application; not scratching irritated skin {05}

» Discontinuing use and checking with physician if irritation persists, or if facial rash or other problems develop {01} {05}

While using this medication, visiting physician regularly for monitoring of serum and urine calcium levels

Checking with physician if skin problem has not improved (usually within 2 to 8 weeks) or if skin condition becomes worse {01} {05}


Side/adverse effects
Signs of potential side effects, especially dermatitis, skin rash, worsening of psoriasis, atrophy of skin, folliculitis, hypercalcemia, and hypercalciuria


General Dosing Information
Calcipotriene is for external use only and not for ophthalmic, oral, or intravaginal use {01}.

Calcipotriene should not be used on the face since it may cause itching and erythema of the facial skin. Patients should be instructed to wash their hands after using calcipotriene to avoid inadvertent transfer of this medication to the face or eyes. Should facial dermatitis develop, therapy should be discontinued {05}.

Excessive use (more than 100 grams of cream or ointment, 60 mL of solution, or a total calcipotriene dose of 5 mg per week) may cause elevated serum or urinary calcium, which rapidly subsides when treatment is discontinued {05} {22}.

For cream and ointment dosage forms
The patient should apply the cream or ointment only to lesions and rub in well. Calcipotriene should be used cautiously in skin folds, such as the intertriginous areas, where natural occlusion may increase the medication's irritant effect {05} {22} {25}.

Treatment with calcipotriene ointment may be combined with ultraviolet light phototherapy. With this form of treatment, patients are allowed to expose their skin to sunlight. Calcipotriene ointment should not be applied the morning of exposure to ultraviolet (UV) light {05} because of the significant UV-blocking action of the vehicle {31}.

For solution dosage form
To properly apply the topical solution to the scalp, the patient should comb dry hair and remove any scaly debris, then part the hair for easy access to scalp lesions. The medication is then applied and gently rubbed thoroughly into visible lesions {30}. Avoid applying to unaffected areas of skin, including forehead {30}.


Topical Dosage Forms

CALCIPOTRIENE CREAM

Usual adult dose
Psoriasis
Topical, to the affected area(s) of skin, two times a day {29}. Efficacy of treatment beyond eight weeks has not been established {05}.


Usual adult prescribing limits
100 grams of cream per week {29}, or a total dose of 5 mg of calcipotriene per week {05} when using more than one formulation.

Usual pediatric dose
Safety and efficacy have not been established {01} {05}.

Usual geriatric dose
See Usual adult dose {29}.

Strength(s) usually available
U.S.—


0.005% (Rx) [Dovonex{01} (cetearyl alcohol) (ceteth-20) (diazolidinyl urea) (dichlorobenzyl alcohol) (dibasic sodium phosphate) (edetate disodium) (glycerin) (mineral oil) (petrolatum) (water)]

Canada—


0.005% (Rx) [Dovonex{05} (cetomacrogol 1000) (chlorallyhexaminium chloride [dowicil 200]) (disodium edetate) (disodium phosphate dihydrate) (glycerol 85%) (liquid paraffin) (purified water) (white soft paraffin)]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F), unless otherwise specified by manufacturer. Protect from freezing {29}.

Auxiliary labeling:
   • For external use only.


CALCIPOTRIENE OINTMENT

Usual adult dose
Psoriasis
Topical, to the affected area(s) of skin, one or two times a day. Efficacy of treatment beyond eight weeks has not been established {05}.


Usual adult prescribing limits
100 grams of ointment per week or a total dose of 5 mg of calcipotriene per week {05} when more than one formulation is used.

Usual pediatric dose
Safety and efficacy have not been established {01} {05}.

Usual geriatric dose
See Usual adult dose {29}.

Strength(s) usually available
U.S.—


0.005% (Rx) [Dovonex{01} (dibasic sodium phosphate) (edetate disodium) (mineral oil) (petrolatum) (propylene glycol) (tocopherol) (steareth-2) (water)]

Canada—


0.005% (Rx) [Dovonex{05} (disodium edetate) (disodium phosphate dihydrate) (D,L-alpha-tocopherol) (liquid paraffin) (polyoxyethylene-(2)-stearyl ether) (propylene glycol) (purified water) (white soft paraffin)]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F), unless otherwise specified by manufacturer. Protect from freezing. {01} {05}

Auxiliary labeling:
   • For external use only.


CALCIPOTRIENE SOLUTION

Usual adult dose
Psoriasis, of scalp
Topical, to the scalp lesions, two times a day {05}. Efficacy of treatment beyond eight weeks has not been established {05} {30}.


Usual adult prescribing limits
60 mL of solution per week {05}, or a total dose of 5 mg of calcipotriene per week when other formulations are used {05}.

Usual pediatric dose
Safety and efficacy have not been established {01} {05}.

Usual geriatric dose
See Usual adult dose {29}.

Strength(s) usually available
U.S.—


0.005% (Rx) [Dovonex (hydroxypropyl cellulose) (isopropanol 51% v/v) (menthol) (propylene glycol) (sodium citrate) (water){30}]

Canada—


0.005% (Rx) [Dovonex{05} (hydroxypropyl cellulose) (isopropanol) (levomenthol) (propylene glycol) (purified water) (sodium citrate)]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F), unless otherwise specified by manufacturer. Protect from freezing. Protect from light {05} {30}.

Auxiliary labeling:
   • For external use only.

Additional information:
This medication contains alcohol and is flammable; keep away from open flame {30}.



Revised: 08/20/1997



References
  1. Dovonex package insert (Westwood-Squibb Pharm—US), Rev 3/97, Rec 5/97.
  1. Bruce S, Epinette WW, Funicella T, et al. Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis. J Am Acad Dermatol 1994; 31(5 Pt 1): 755-9.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1997. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1996. p. 120.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 31st ed. London: The Pharmaceutical Press; 1996. p. 1083.
  1. Dovonex (Leo). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 31st ed. Ottawa: Canadian Pharmaceutical Association; 1996. p. 489-90.
  1. Cunliffe WJ, Berth-Jones J, Claudy A, et al. Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris. J Am Acad Dermatol 1992; 26(5 Pt 1): 736-43.
  1. Kragballe K, Gjertsen BT, De Hoop D, et al. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991; 337: 193-6.
  1. Dubertret L, Wallach D, Souteyrand P, et al. Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. J Am Acad Dermatol 1992; 27(6 Pt 1): 983-8.
  1. Bourke JF, Berth-Jones J, Iqbal SJ, et al. High-dose topical calcipotriol in the treatment of extensive psoriasis vulgaris. Br J Dermatol 1993; 129: 74-6.
  1. Mozzanica N, Cattaneo A, Schmitt E, et al. Topical calcipotriol for psoriasis—an immunohistologic study. Acta Derm Venereol (Stockh) 1994; 74(Suppl 186): 171-2.
  1. Cagnoni ML, Ghersetich I, Lotti T, et al. Treatment of psoriasis vulgaris with topical calcipotriol: Is the clinical improvement of lesional skin related to a down-regulation of some cell adhesion molecules? Acta Derm Venereol (Stockh) 1994; 74(Suppl 186): 55-7.
  1. Berth-Jones J, Bourke JF, Iqbal SJ, et al. Urine calcium excretion during treatment of psoriasis. Br J Dermatol 1993; 129(4): 411-4.
  1. McKenna KE, Burrows D. Hypercalciuria and topical calcipotriol therapy. Br J Dermatol 1994; 131: 588.
  1. Hoeck HC, Laurberg G, Laurberg P. Hypercalcaemic crisis after excessive topical use of vitamin D derivative. J Intern Med 1994; 235: 281-2.
  1. Russell S, Young MJ. Hypercalcemia during treatment of psoriasis with calcipotriol. Br J Dermatol 1994; 130: 795-6.
  1. Palleschi GM, Gentili A, Caproni M, et al. Structural alterations of basal keratinocytes and capillary loop in psoriasis during treatment with topical calcipotriol. Acta Derm Venereol (Stockh) 1994; 74(Suppl 186): 49-51.
  1. De Groot AC. Contact allergy to calcipotriol. Contact Dermatitis 1994; 30: 242-3.
  1. Steinkjer B. Contact dermatitis from calcipotriol. Contact Dermatitis 1994; 31: 122.
  1. Rigopoulos D, Aroni K. Stratigos JT. Generalized pustular psoriasis precipitated by topical calcipotriol cream. Int J Dermatol 1994; 33: 515-6.
  1. Murdoch D, Clissold SP. Calcipotriol. A review of its pharmacological properties and therapeutic use in psoriasis vulgaris. Drugs 1992; 43(3): 415-29.
  1. Highton A, Quell J, The Calcipotriene Study Group. Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study. J Am Acad Dermatol 1995; 32(1): 67-72.
  1. Panel comment, 4/94.
  1. Schroeder SA, Krupp MA, Tierney LM Jr, et al, editors. Current medical diagnosis and treatment 1990. East Norwalk, CT: Appleton and Lange; 1990. p. 784-8.
  1. Reviewers' consensus on Calcipotriene (Topical) monograph draft of 3/95.
  1. Panel comment, 3/95.
  1. Panel comment, 3/95
  1. Panel comment, 3/95.
  1. Berkow R, editor. The Merck manual of diagnosis and therapy. 16th ed. Rahway, NJ: Merck Research Laboratories; 1992. p. 1012-3.
  1. Dovonex cream package insert (Westwood-Squibb Pharm—US), Developed 1996, Rec 5/97.
  1. Dovonex solution package insert (Westwood-Squibb Pharm—US), Rev 2/97, Rec 5/97.
  1. Speight EI, Farr PM. Calcipotriol improves the response of psoriasis to PUVA. Br J Dermatol 1994; 130(6): 79-82.
  1. Orange AP, Marcoux D, Svensson A, et al. Topical calcipotriol in childhood psoriasis. J Am Acad Dermatol 1997; 36: 203-8.
  1. Reichrath J, Muller SM, Kerber A, et al. Biologic effect of topical calcipotriol (MC 903) treatment in psoriatic skin. J Am Acad Dermatol 1997; 36: 19-28.
  1. Manufacturer comment, 5/97.
  1. Panel comments, 7/97.
  1. Lebwohl M, Hecker D, Martinez J, et al. Interactions between calcipotriene and ultraviolet light. J Am Acad Dermatol 1997; 37: 93-5.
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