Dovonex Information
Dovonex (Calcipotriol) Description
Dovonex (Calcipotriol) (calcipotriene ointment), 0.005% contains the compound calcipotriene, a synthetic vitamin D derivative for topical dermatological use.
Chemically, calcipotriene is (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1α,3β,24-triol-, with the empirical formula CHO, a molecular weight of 412.6, and the following structural formula:
Calcipotriene is a white or off-white crystalline substance. Dovonex (Calcipotriol) ointment contains calcipotriene 50 µg/g in an ointment base of dibasic sodium phosphate, edetate disodium, mineral oil, petrolatum, propylene glycol, tocopherol, steareth-2 and water.
Dovonex (Calcipotriol) 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 (cholecalciferol) in the skin. Calcipotriene is a synthetic analog of vitamin D.
Clinical studies with radiolabelled ointment indicate that approximately 6% (± 3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (± 2.6%, SD) when applied to normal skin, and much of the absorbed active 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 (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 (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.
Dovonex (Calcipotriol) Clinical Studies
Adequate and well-controlled trials of patients treated with Dovonex (Calcipotriol) ointment have demonstrated improvement usually beginning after two weeks of therapy. This improvement continued in patients using Dovonex (Calcipotriol) once daily and twice daily. After 8 weeks of once daily Dovonex (Calcipotriol) , 56.7% of patients showed at least marked improvements (6.4% showed complete clearing). After 8 weeks of twice daily Dovonex (Calcipotriol) , 70.0% of patients showed at least marked improvement (11.3% showed complete clearing).
Subtracting percentages of patients using placebo (vehicle only) from percentages of patients using Dovonex (Calcipotriol) who had at least marked improvements after 8 weeks yields 39.9% for once daily and 49.6% for twice daily. This adjustment for placebo effect indicates that what might appear to be differences between once and twice daily use may reflect differences in the studies independent from the frequency of dosing. Although there was a numerical difference in comparison across studies, twice daily dosing has not been shown to be superior in efficacy to once daily dosing.
Over 400 patients have been treated in open label clinical studies of Dovonex (Calcipotriol) for periods of up to one year. In half of these studies, patients who previously had not responded well to Dovonex (Calcipotriol) were excluded. The adverse events in these extended studies included skin irritation in approximately 25% of patients and worsening of psoriasis in approximately 10% of patients. In one of these open label studies, half of the patients no longer required Dovonex (Calcipotriol) by 16 weeks of treatment, because of satisfactory therapeutic results.
Dovonex (Calcipotriol) Indications And Usage
Dovonex (Calcipotriol) (calcipotriene ointment), 0.005%, is indicated for the treatment of plaque psoriasis in adults. The safety and effectiveness of topical calcipotriene in dermatoses other than psoriasis have not been established.
Dovonex (Calcipotriol) Contraindications
Dovonex (Calcipotriol) is contraindicated in those patients with 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. Dovonex (Calcipotriol) should not be used on the face.
Dovonex (Calcipotriol) Precautions
Use of Dovonex (Calcipotriol) may cause irritation of lesions and surrounding uninvolved skin. If irritation develops, Dovonex (Calcipotriol) 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 (Calcipotriol) . If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored.
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 (Calcipotriol) 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 (Calcipotriol) .
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/m/day) of calcipotriene indicated no impairment of fertility or general reproductive performance.
Dovonex (Calcipotriol) Adverse Reactions
In controlled clinical trials, the most frequent adverse reactions reported for Dovonex (Calcipotriol) were burning, itching and skin irritation, which occurred in approximately 10-15% of patients. Erythema, dry skin, peeling, rash, dermatitis, worsening of psoriasis including development of facial/scalp psoriasis were reported in 1 to 10% of patients. Other experiences reported in less than 1% of patients included skin atrophy, hyperpigmentation, hypercalcemia, and folliculitis. Once daily dosing has not been shown to be superior in safety to twice daily dosing.
Dovonex (Calcipotriol) Overdosage
Topically applied Dovonex (Calcipotriol) can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of Dovonex (Calcipotriol) ointment.
Dovonex (Calcipotriol) Dosage And Administration
Apply a thin layer of Dovonex (Calcipotriol) ointment once or twice daily and rub in gently and completely.
Dovonex (Calcipotriol) How Supplied
Dovonex (Calcipotriol) (calcipotriene ointment), 0.005% is available in:
60 gram aluminum tubes (NDC 0072-2540-06).120 gram aluminum tubes (NDC 0072-2540-12).
Dovonex (Calcipotriol)
