Dovonex® (calcipotriene solution) Scalp Solution, 0.005% is a colorless topical solution containing 0.005% calcipotriene in a vehicle of isopropanol (51% v/v), propylene glycol, hydroxypropyl cellulose, sodium citrate, menthol and water.

The chemical name of calcipotriene is (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola- 5,7,10(19),22tetraene-1α,3β,24-triol, with the empirical formula C₂₇H₄₀O₃, a molecular weight of 412.6, and the following structural formula:

Last updated on RxList: 6/2/2009

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.

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.

Dovonex® (calcipotriene solution) Scalp Solution, 0.005% is available in 60 mL plastic bottles N 0430-3030-15

Storage

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

Manufactured by : LEO Pharmaceutical Products, Ltd., Ballerup, Denmark. Marketed by: Warner Chilcott (US), Inc., Rockaway, NJ 07866 USA.

Last updated on RxList: 6/2/2009

In controlled clinical trials, the most frequent adverse reactions reported to be related to Dovonex® Scalp Solution, 0.005%, use were transient burning, stinging and tingling, which occurred in approximately 23% of patients. Rash was reported in about 11% of patients. Dry skin, irritation and worsening of psoriasis were reported in 1-5% of patients. Skin atrophy, hyperpigmentation, hypercalcemia, and folliculitis were not observed in these studies, but cannot be excluded.

No information provided.

Last updated on RxList: 6/2/2009

Avoid contact with the eyes or mucous membranes. Discontinue use if a sensitivity reaction occurs or if excessive irritation develops on uninvolved skin areas.

Drug product is flammable. Keep away from open flame.

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.

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 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/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. Increased rabbit maternal and fetal toxicity was noted at 12 μg/kg/day (132 μg/m²/day). Rabbits administered 36 μg/kg/day (396 μg/m²/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/m²/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/m²/day) and rabbit (17.6 μg/m²/day) studies are greater than the expected human systemic exposure level (0.13 μg/m²/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 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. 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 skinrelated 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.

Last updated on RxList: 6/2/2009

Topically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of topical calcipotriene. If elevation in serum calcium should occur, discontinue treatment until normal calcium levels are restored. (See PRECAUTIONS.)

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.

Last updated on RxList: 6/2/2009

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.

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 cm²) 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 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® 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.

Last updated on RxList: 6/2/2009

Patients using Dovonex® Scalp Solution, 0.005%, should receive the following information and instructions:

1. 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.
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 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: 6/2/2009

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 SCALP SOLUTION - TOPICAL

(kal-SIP-oh-try-een)

COMMON BRAND NAME(S): Dovonex

USES: This medication is used to treat long-term psoriasis of the scalp. 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. Comb the hair first to remove any scaly flakes. Apply the medication only to the affected areas of the scalp and gently rub in, usually twice daily or as directed by your doctor. Take care not to let any of the solution spread onto the forehead or any unaffected area. Wash your hands after using. 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 times 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, stinging, tingling, rash, dry skin, or irritation 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), sudden worsening of psoriasis.

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.

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 sunlight or open flames. 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.