No information provided.
Use of Dovonex® (calcipotriene ointment) may cause irritation of lesions and surrounding uninvolved skin. If irritation develops, Dovonex® (calcipotriene ointment) 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® (calcipotriene ointment) . If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored.
Carcinogenesis, Mutagenesis, Impairment of Fertility
When calcipotriene was applied topically to mice for up to 24 months at dosages
of 3, 10 and 30 Âµg/kg/day (corresponding to 9, 30 and 90 Âµg/m2/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® (calcipotriene ointment) 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 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/m2/day)
of calcipotriene indicated no impairment of fertility or general reproductive
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® (calcipotriene ointment) ointment
should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
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.
Safety and effectiveness of Dovonex® (calcipotriene ointment) 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.
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).