Dovonex® (calcipotriene ointment), 0.005% contains the compound calcipotriene, a synthetic vitamin D3 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 C₂₇H₄₀O₃, a molecular weight of 412.6, and the following structural formula:

Calcipotriene is a white or off-white crystalline substance. Dovonex® 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.

Last updated on RxList: 5/6/2008

Dovonex® (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.

Apply a thin layer of Dovonex® ointment once or twice daily and rub in gently and completely.

Dovonex® (calcipotriene ointment), 0.005% is available in:

60 gram aluminum tubes N 0430-3010-15
120 gram aluminum tubes N 0430-3010-17

Storage

Store at controlled room temperature 15° C - 25° C (59° F - 77° F). Do not freeze.

Manufactured by LEO Laboratories Ltd. Dublin, Ireland. Marketed by: Warner Chilcott (US), Inc. Rockaway, NJ 07866 USA. 1-800-521-8813. Revised November 2007. FDA Rev date: 9/26/2007

Last updated on RxList: 5/6/2008

In controlled clinical trials, the most frequent adverse reactions reported for Dovonex® 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.

No information provided.

Last updated on RxList: 5/6/2008

No information provided.

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.

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/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® 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 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).

Last updated on RxList: 5/6/2008

Topically applied Dovonex® can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of Dovonex® ointment.

Dovonex® 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® should not be used on the face.

Last updated on RxList: 5/6/2008

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 D₃ (cholecalciferol) in the skin. Calcipotriene is a synthetic analog of vitamin D₃.

Clinical studies with radiolabelled calcipotriene 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 D3 (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 D3 (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® ointment have demonstrated improvement usually beginning after two weeks of therapy. This improvement continued in patients using Dovonex® once daily and twice daily. After 8 weeks of once daily Dovonex®, 56.7% of patients showed at least marked improvements (6.4% showed complete clearing). After 8 weeks of twice daily Dovonex®, 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® 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 daily 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® for periods of up to one year. In half of these studies, patients who previously had not responded well to Dovonex® 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® by 16 weeks of treatment, because of satisfactory therapeutic results.

Last updated on RxList: 5/6/2008

Patients using Dovonex® should receive the following information and instructions:

1. 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.
2. This medication should not be used for any disorder other than that for which it was prescribed.
3. Patients should report to their physician any signs of local adverse reactions.
4. 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.).

Last updated on RxList: 5/6/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CALCIPOTRIENE - TOPICAL

(kal-SIP-oh-try-een)

COMMON BRAND NAME(S): Dovonex

USES: This medication is used to treat psoriasis. Calcipotriene is a form of vitamin D. It works by slowing down the growth of skin cells.

HOW TO USE: Use this medication on the skin only. Apply a thin layer of the medication to the affected area and gently rub in, usually once or twice daily for the ointment or twice daily for the cream or as directed by your doctor. Wash your hands after using, unless you are using this medication to treat the hands. Do not apply the medication on the face, in the eyes, nose, or mouth, or inside the vagina. If you do get the medication in those areas, flush with plenty of water.

Do not apply more often or use longer than prescribed. This may increase the risk of side effects.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time(s) each day.

Inform your doctor if your condition does not improve or if it worsens. You should usually begin to see an improvement in your skin condition after 2 weeks of treatment.

SIDE EFFECTS: Burning, itching, rash, irritation, redness, dry skin, or peeling at the application site may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: skin thinning/discoloration, stretch marks, "hair bumps" (folliculitis), unusual tiredness, mental/mood changes, unexplained constipation.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: high calcium/vitamin D levels (hypercalcemia/hypervitaminosis D).

Before using this medication, tell your doctor or pharmacist your medical history.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors. Your doctor may direct you to limit or avoid phototherapy while you use this medication. Discuss this further with your doctor.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other products containing vitamin D.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If overdose or swallowing is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., calcium levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

This medication has been prescribed for your current condition only. Do not use it later for another skin condition unless told to do so by your doctor. A different medication may be necessary in that case.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 59-77 degrees F (15-25 degrees C) away from light. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.