PRECAUTIONS
General
Use of Dovonex may cause irritation of lesions and surrounding uninvolved skin. If irritation develops, Dovonex should be discontinued.
For external use only. Keep out of the reach of children. Always wash hands thoroughly after use.
Transient, rapidly reversible elevation of serum calcium has occurred with use of Dovonex. 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 should receive the following information and instructions:
- This medication is to be used 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 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 local 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
The potential of calcipotriene to induce carcinogenesis in standard long-term animal studies (in the absence of ultraviolet radiation [UVR]) has not been evaluated. 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 (318 µg/m2/day) of calcipotriene indicated no impairment of fertility or general reproductive performance.
Pregnancy
Teratogenic 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. In rabbits, increased maternal and fetal toxicity were noted at a dosage of 12 µg/kg/day (132 µg/m2/day); a dosage of 36 µg/kg/day (396 µg/m2/day) resulted in a significant increase in the incidence of incomplete ossification of the pubic bones and forelimb phalanges of fetuses. In a rat study, a dosage of 54 µg/kg/day (318 µg/m2/day) resulted in a significantly increased incidence of skeletal abnormalities (enlarged fontanelles and extra ribs). The enlarged fontanelles are most likely due to calcipotriene's effect upon calcium metabolism. The estimated maternal and fetal no-effect exposure levels in the rat (43.2 µg/m2/day) and rabbit (17.6 µg/m2/day) studies are approximately equal to the expected human systemic exposure level (18.5 µg/m2/day) from dermal application. There are no adequate and well-controlled studies in pregnant women. Therefore, Dovonex ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether calcipotriene is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Dovonex (calcipotriene ointment), 0.005% is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of Dovonex in pediatric patients have not been 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 ointment, approximately 12% were 65 or older, while approximately 4% were 75 and over. The results of an analysis of severity of skin-related adverse events showed a statistically significant difference for subjects over 65 years (more severe) compared to those under 65 years (less severe).
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