Document
DailyMed Label: Dovonex
Title
DailyMed Label: Dovonex
Date
2009
Document type
DailyMed Prescription
Name
Dovonex
Generic name
Calcipotriene
Manufacturer
Physicians Total Care, Inc.
Product information
NDC: 54868-6057
Product information
NDC: 54868-6057
Description
Dovonex ® (calcipotriene solution) Scalp
Solution, 0.005% is a colorless topical solution containing calcipotriene
monohydrate, a synthetic vitamin D 3 derivative, for
topical dermatologic use. Chemically, calcipotriene monohydrate is
(5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1α,3β,24-triol
monohydrate, with the empirical formula C 27 H 40 O 3 ·H 2 O, a
molecular weight of 430.6, and the following structural formula:
Calcipotriene monohydrate is a white or off-white crystalline substance.
Dovonex ® Scalp Solution contains calcipotriene
monohydrate equivalent to 50 μg/g anhydrous calcipotriene in a vehicle of
isopropanol (51% v/v), propylene glycol, hydroxypropyl cellulose, sodium
citrate, menthol and water.
image of chemical structure
Indications
Dovonex ® (calcipotriene solution) Scalp Solution,
0.005%, is indicated for the topical treatment of chronic, moderately severe
psoriasis of the scalp. The safety and effectiveness of topical calcipotriene in
dermatoses other than psoriasis have not been established.
Dosage
Comb the hair to remove scaly debris and after suitably parting,
apply Dovonex ® Scalp Solution, 0.005%, twice daily, only
to the lesions, and rub in gently and completely, taking care to prevent the
solution spreading onto the forehead. The safety and efficacy of Dovonex ® Scalp Solution, 0.005%, have been demonstrated in patients
treated for eight weeks.
Keep Dovonex ® Scalp Solution, 0.005%,
well away from the eyes . Avoid application of the solution to uninvolved
scalp margins. Always wash hands thoroughly after use.
Contraindications
Dovonex ® Scalp Solution, 0.005%, is contraindicated in
those patients with acute psoriatic eruptions or a history of hypersensitivity
to any of the components of the preparation. It should not be used by patients
with demonstrated hypercalcemia or evidence of vitamin D toxicity.
Precautions
General
Use of Dovonex ® Scalp Solution, 0.005%,
may cause transient irritation of both lesions and surrounding uninvolved skin.
If irritation develops, Dovonex ® Scalp Solution, 0.005%,
should be discontinued.
For external use only. Keep out of the reach of children. Always wash hands
thoroughly after use.
Reversible elevation of serum calcium has occurred with use of topical
calcipotriene. If elevation in serum calcium outside the normal range should
occur, discontinue treatment until normal calcium levels are restored. Information
for Patients
Patients using Dovonex ® Scalp Solution, 0.005%, should
receive the following information and instructions:
This medication is to be used only as directed by the physician. It is for
external use only. Avoid contact with the face or eyes. As with any topical
medication, patients should wash their hands after application.
This medication should not be used for any disorder other than that for
which it was prescribed.
Patients should report to their physician any signs of adverse reactions.
Patients that apply Dovonex ® to exposed portions of
the body should avoid excessive exposure to either natural or artificial
sunlight (including tanning booths, sun lamps, etc.).
Carcinogenesis,
Mutagenesis, Impairment of Fertility
When calcipotriene was applied topically to mice for up to 24 months at
dosages of 3, 10 and 30 μg/kg/day (corresponding to 9, 30 and 90 μg/m 2 /day), no significant changes in tumor incidence were observed
when compared to control. In a study in which albino hairless mice were exposed
to both UVR and topically applied calcipotriene, a reduction in the time
required for UVR to induce the formation of skin tumors was observed
(statistically significant in males only), suggesting that calcipotriene may
enhance the effect of UVR to induce skin tumors. Patients that apply
Dovonex ® to exposed portions of the body should avoid
excessive exposure to either natural or artificial sunlight (including tanning
booths, sun lamps, etc.). Physicians may wish to limit or avoid use of
phototherapy in patients that use Dovonex ® .
Calcipotriene did not elicit any mutagenic effects in an Ames mutagenicity
assay, a mouse lymphoma TK locus assay, a human lymphocyte chromosome aberration
assay, or in a micronucleus assay conducted in mice.
Studies in rats at doses up to 54 μg/kg/day (324 μg/m 2 /day) of calcipotriene indicated no impairment of fertility or
general reproductive performance. PregnancyTeratogenic
Effects: Pregnancy Category C
Studies of teratogenicity were done by the oral route where bioavailability
is expected to be approximately 40-60% of the administered dose. Increased
rabbit maternal and fetal toxicity was noted at 12 μg/kg/day (132 μg/m 2 /day). Rabbits administered 36 μg/kg/day (396 μg/m 2 /day) resulted in fetuses with a significant increase in the
incidences of pubic bones, forelimb phalanges, and incomplete bone ossification.
In a rat study, oral doses of 54 μg/kg/day (318 μg/m 2 /day) resulted in a significantly higher incidence of skeletal
abnormalities consisting primarily of enlarged fontanelles and extra ribs. The
enlarged fontanelles are most likely due to calcipotriene's effect upon calcium
metabolism. The maternal and fetal calculated no-effect exposures in the rat
(43.2 μg/m 2 /day) and rabbit (17.6 μg/m 2 /day) studies are greater than the expected human systemic
exposure level (0.13 μg/m 2 /day) from dermal application.
There are no adequate and well-controlled studies in pregnant women. Therefore,
Dovonex ® Scalp Solution, 0.005%, should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus. Nursing
Mothers
There is evidence that maternal 1,25-dihydroxy vitamin D 3 (calcitriol) may enter the fetal circulation, but it is not
known whether it is excreted in human milk. The systemic disposition of
calcipotriene is expected to be similar to that of the naturally occurring
vitamin. Because many drugs are excreted in human milk, caution should be
exercised when Dovonex ® (calcipotriene solution) Scalp
Solution, 0.005%, is administered to a nursing woman. Pediatric
Use
Safety and effectiveness of Dovonex ® Scalp Solution,
0.005%, in pediatric patients have not been specifically established. Because of
a higher ratio of skin surface area to body mass, pediatric patients are at
greater risk than adults of systemic adverse effects when they are treated with
topical medication. Geriatric
Use
Of the total number of patients in clinical studies of calcipotriene
solution, approximately 16% were 65 or older, while approximately 4% were 75 and
over. The results of an analysis of severity of skin-related adverse events
showed no differences for subjects over 65 years compared to those under 65
years, but greater sensitivity of some older individuals cannot be ruled out.
Adverse reactions
In controlled clinical trials, the most frequent adverse reactions reported to
be related to Dovonex
How supplied
Dovonex ® (calcipotriene solution) Scalp Solution, 0.005%
is available in 60 mL plastic bottles, NDC 54868-6057-0
STORAGE
Store at controlled room temperature 15° C - 25° C (59° F - 77° F). Avoid
sunlight. Do not freeze.
Clinical pharmacology
In humans, the natural supply of vitamin D depends mainly on
exposure to the ultraviolet rays of the sun for conversion of
7-dehydrocholesterol to vitamin D 3 (cholecalciferol) in
the skin. Calcipotriene is a synthetic analog of vitamin D 3 .
Although the precise mechanism of calcipotriene’s antipsoriatic action is not
fully understood, in vitro evidence suggests that
calcipotriene is roughly equipotent to the natural vitamin in its effects on
proliferation and differentiation of a variety of cell types. Calcipotriene has
also been shown, in animal studies, to be 100-200 times less potent in its
effects on calcium utilization than the natural hormone.
Clinical studies with radiolabelled calcipotriene solution indicate that less
than 1% of the applied dose of calcipotriene is absorbed through the scalp when
the solution (2.0 mL) is applied topically to normal skin or psoriasis plaques
(160 cm 2 ) for 12 hours, and that much of the absorbed
calcipotriene is converted to inactive metabolites within 24 hours of
application.
Vitamin D and its metabolites are transported in the blood, bound to specific
plasma proteins. The active form of the vitamin, 1,25-dihydroxy vitamin D 3 (calcitriol), is known to be recycled via the liver and
excreted in the bile. Calcipotriene metabolism following systemic uptake is
rapid, and occurs via a similar pathway to the natural hormone. The primary
metabolites are much less potent than the parent compound.
There is evidence that maternal 1,25-dihydroxy vitamin D 3 (calcitriol) may enter the fetal circulation, but it is not
known whether it is excreted in human milk. The systemic disposition of
calcipotriene is expected to be similar to that of the naturally occurring
vitamin.
Clinical studies
Adequate and well-controlled trials of patients treated with Dovonex ® Scalp Solution, 0.005%, have demonstrated improvement usually
beginning after 2 weeks of therapy. This improvement continued with
approximately 31% of patients appearing either cleared (14%) or almost cleared
(17%) after 8 weeks of therapy.
Package label
Dovonex ® (calcipotriene solution) Scalp Solution, 0.005%
image of barcode package label
1 organization
1 product
Product
Taclonex ScalpOrganization
Physicians Total Care, Inc.