TACLONEX (calcipotriene 0.005% and betamethasone dipropionate 0.064%)OINTMENT  

FOR TOPICAL USE ONLY.

Not for Ophthalmic, Oral or Intravaginal Use.

Taclonex Ointment contains calcipotriene hydrate and betamethasone dipropionate. It is intended for topical use.

Calcipotriene hydrate is a synthetic vitamin D analogue.

Chemically, calcipotriene hydrate is (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1(α),3(β),24-triol,hydrate, with the empirical formula CHO,HO, a molecular weight of 430.6, and the following structural formula:

Calcipotriene hydrate is a white to almost white crystalline compound.

Betamethasone dipropionate is a synthetic corticosteroid.

Betamethasone dipropionate has the chemical name 9-fluoro-11(β),17,21-trihydroxy-16(β)-methylpregna-1,4-diene-3,20-dione17,21-dipropionate, with the empirical formula CHFO, a molecular weight of 504.6, and the following structural formula:

Betamethasone dipropionate is a white to almost white odorless powder.

Each gram of Taclonex Ointment contains 52.18 mcg of calcipotriene hydrate (equivalent to 50 mcg of calcipotriene) and 0.643 mg of betamethasone dipropionate (equivalent to 0.5 mg of betamethasone) in an ointment base of mineral oil, PPG-15 stearyl ether, dl-alpha tocopherol and white petrolatum.

Taclonex Ointment:

Taclonex Ointment combines the pharmacological effects of calcipotriene hydrate and betamethasone dipropionate as described below.

In a vasoconstrictor study, the skin blanching response of Taclonex Ointment was consistent with that of a potent corticosteroid.

Calcipotriene

Pharmacokinetics: Calcipotriene metabolism following systemic uptake is rapid and occurs in the liver. The primary metabolites of calcipotriene are less potent than the parent compound.

Betamethasone dipropionate

Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic and vasoconstrictive properties. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in psoriasis vulgaris are uncertain.

Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Taclonex Ointment was applied once daily for 4 weeks to adult patients (N = 12) with psoriasis vulgaris to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. Of eleven patients tested, none demonstrated adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL.

However in another clinical study of Taclonex Ointment, one subject (N = 19) demonstrated adrenal suppression.

In an international, multi-center, double-blind, vehicle- and active-controlled, parallel-group study, 1,603 patients with mild to very severe psoriasis vulgaris on trunk and limbs were treated once daily for 4 weeks. Patients were randomized to one of four treatment arms: Taclonex Ointment, calcipotriene hydrate 50 mcg/g in the same vehicle, betamethasone dipropionate 0.64 mg/g in the same vehicle, and vehicle alone. The mean age of the patients was 48.4 years and 60.5% were male. Most patients had disease of moderate severity at baseline.

Efficacy was assessed as the proportion of patients with absent or very mild disease according to the Investigator’s Global Assessment of Disease Severity at end of treatment (4 weeks). “Absent” disease was defined as no evidence of redness, thickness, or scaling. “Very mild disease” was defined as controlled disease, but not entirely cleared: lesions with some discoloration with absolutely minimal thickness, i.e. the edges to the lesion(s) could just be felt.

In addition to the pivotal study (N = 490), four randomized, double-blind, vehicle- or active-controlled, parallel-group studies were conducted and provided supportive evidence of efficacy. These studies included a total of 1,058 patients treated with Taclonex Ointment once daily for up to 4 weeks.

Taclonex Ointment is indicated for the topical treatment of psoriasis vulgaris in adults 18 years of age and above for up to 4 weeks. The maximum weekly dose should not exceed 100 g. Treatment of more than 30% body surface area is not recommended.

Taclonex Ointment should not be applied to the face, axillae or groin.

Taclonex Ointment is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Taclonex Ointment is contraindicated in patients with known or suspected disorders of calcium metabolism.

Taclonex Ointment is contraindicated in patients with erythrodermic, exfoliative and pustular psoriasis. 

Hypercalcemia has been observed with use of TaclonexOintment. If elevation of serum calcium outside the normal range occurs, discontinue treatment until normal calcium levels are restored. In the trials that included assessment of the effects of TaclonexOintment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Taclonex Ointment on calcium metabolism following treatment durations of longer than 4 weeks are not known.

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. (See DOSAGE AND ADMINISTRATION .)

Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area should be eva luated periodically for evidence of HPA axis suppression by using the Cosyntropin Stimulation Test. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid.

The use of Taclonex Ointment has not been studied in patients with severe renal insufficiency or severe hepatic disorders.

HPA axis suppression has been observed with TaclonexOintment.

If irritation develops, Taclonex Ointment should be discontinued and appropriate therapy instituted.

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than by noting any clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop after treatment initiations, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Taclonex Ointment should be discontinued until the infection has been adequately controlled.

Taclonex Ointment should not be used in the presence of pre-existing skin atrophy at the treatment site.

Taclonex Ointment should not be used on the face, axillae or groin.

This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Patients using Taclonex Ointment should receive the following information and instructions.

See PRECAUTIONS , General .

When calcipotriene was applied topically to mice for up to 24 months at dosages of 3, 10 and 30 mcg/kg/day (corresponding to 9, 30 and 90 mcg/m/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 ultra-violet radiation (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 who apply Taclonex 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 limit or avoid use of phototherapy in patients that use Taclonex Ointment.

Long-term animal studies have not been performed to eva luate the carcinogenic potential of betamethasone dipropionate.

Calcipotriene did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, the human lymphocyte chromosome aberration test, or the mouse micronucleus test.

Betamethasone dipropionate did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, or in the rat micronucleus test.

Studies in rats with oral doses of up to 54 mcg/kg/day (324 mcg/m/day) of calcipotriene demonstrated no impairment of fertility or general reproductive performance.

Studies in rats with oral doses of up to 0.2 mg/kg/day (1,200 mcg/m/day) of betamethasone dipropionate demonstrated no impairment of male fertility.

Animal reproduction studies have not been conducted with Taclonex Ointment. Taclonex Ointment contains calcipotriene that has been shown to be fetotoxic and betamethasone dipropionate that has been shown to be teratogenic in animals when given systemically. There are no adequate and well-controlled studies in pregnant women. Taclonex Ointment should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.

Teratogenicity studies with calcipotriene were performed by the oral route in rats and rabbits. In rabbits, increased maternal and fetal toxicity were noted at dosage of 12 mcg/kg/day (144 mcg/m/day); a dosage of 36 mcg/kg/day (432 mcg/m/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 mcg/kg/day (324 mcg/m/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 levels in the rat (108 mcg/m/day) and rabbit (48 mcg/m/day) studies are lower than the estimated maximum topical dose in man (approximately 460 mcg/m/day). Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Betamethasone dipropionate has been shown to be teratogenic in mice and rabbits when given by the subcutaneous route at doses of 156 mcg/kg/day (468 mcg/m/day) and 2.5 mcg/kg/day (30 mcg/m/day), respectively. Those dose levels are lower than the estimated maximum topical dose in man (5,948 mcg/m/day). The abnormalities observed included umbilical hernia, exencephaly and cleft palates.

Pregnant women were excluded from the clinical trials conducted with TaclonexOintment.

Safety of the use of Taclonex Ointment during lactation has not been established.

Nursing women were excluded from the clinical trials conducted with TaclonexOintment.

It is not known whether topically administered calcipotriene is excreted in human milk.

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk.

Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant.

Because many drugs are excreted in human milk, caution should be exercised when Taclonex Ointment is administered to a nursing woman.

Safety and effectiveness of Taclonex 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 subjects in clinical studies of Taclonex Ointment, approximately 14% were 65 years and older, while approximately 3% were 75 years and over.

No overall differences in safety or effectiveness of Taclonex Ointment were observed between these subjects and younger subjects. All other reported clinical experience has not identified any differences in response between elderly and younger patients.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The data described below reflect exposure to TaclonexOintment in 2,448 patients, including 1,992 exposed for 4 weeks, and 289 exposed for 8 weeks. In the trials that included assessment of the effects of Taclonex Ointment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Taclonex Ointment on calcium metabolism following treatment durations of longer than 4 weeks are not known (see PRECAUTIONS ). The effects of TaclonexOintment on the HPA axis following treatment durations of longer than 4 weeks have not been adequately studied. TaclonexOintment was studied primarily in placebo- and active-controlled trials (N = 1,176, and N = 1,272, respectively). The population was 15 - 97 years old, 61% males and 39% females, mostly white (97%) and had a baseline disease severity ranging from mild to very severe. Most patients received once daily application, and the median weekly dose was 24.5 g.

The percentage of subjects reporting at least one adverse event was 27.1% in the Taclonex Ointment group, 33.0% in the calcipotriene group, 28.3% in the betamethasone group, and 33.4% in the vehicle group.

A lesional/perilesional adverse event was generally defined as an adverse event located ≤ 2 cm from the lesional border.

For subjects who reported lesional/perilesional adverse events, the median time to onset was 7 days for Taclonex Ointment, 7 days for calcipotriene, 5 days for betamethasone dipropionate, and 3 days for vehicle.

Other less common reactions (less than 1% but more than 0.1%) were, in decreasing order of incidence, folliculitis, rash papular, rash pustular, and skin hypopigmentation. Skin atrophy, telangiectasia and skin hyperpigmentation were reported infrequently (0.1%).

In a separate study, patients (N = 207) with at least moderate disease severity were given Taclonex Ointment intermittently on an “as needed” basis for up to 52 weeks. The median use was 15.4 g per week. The effects of Taclonex Ointment on calcium metabolism were not studied and the effects on the HPA axis were not adequately studied. The following adverse reactions were reported by 1% or more of the patients: pruritus (7.2%), psoriasis (3.4%), skin atrophy (1.9%), folliculitis (1.4%), burning sensation (1.4%), skin depigmentation (1.4%), ecchymosis (1.0%), erythema (1.0%) and hand dermatitis (1.0%). One case of a serious flare-up of psoriasis was reported.

Development of pustular psoriasis has been reported as an adverse reaction during and following use of Taclonex Ointment.

Topically applied Taclonex Ointment can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS .)

Apply an adequate layer of Taclonex Ointment to the affected area(s) once daily for up to 4 weeks. Taclonex Ointment should be rubbed in gently and completely. The maximum weekly dose should not exceed 100 g. Treatment of more than 30% body surface area is not recommended. TaclonexOintment should not be applied to the face, axillae or groin.

Taclonex Ointment (calcipotriene 0.005% and betamethasone dipropionate 0.064%) is available in 60 gram collapsible tubes (NDC 0430-3230-15) and 100 gram collapsible tubes (NDC 0430-3230-16).

Store Taclonex Ointment between 20 - 25° C (68 - 77° F); excursions permitted between 15 - 30° C (59 - 86° F).

Keep out of reach of children.

Taclonex Ointment

(calcipotriene 0.005% and betamethasone dipropionate 0.064%)

Read the Patient Information that comes with TaclonexOintment before you start using it and each time you use the ointment. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or treatment.

What is Taclonex Ointment and what is it used for?

Taclonex Ointment is a prescription medicine called a topical (skin-use only).

Taclonex Ointment is used on the skin to treat psoriasis vulgaris in adults.

Taclonex Ointment contains

It is very important that you use Taclonex Ointment only as directed, in order to avoid serious side effects.

Taclonex Ointment is not recommended for use in children. Taclonex Ointment has not been studied in patients under the age of 18.

Who should not use Taclonex Ointment?

Do not use Taclonex Ointment if you:

What should I tell my doctor before using Taclonex Ointment?

Tell your doctor about all of your health conditions, including if you:

Tell your doctor about all the medicines you take, including prescription, and nonprescription medicines, vitamins and herbal supplements. Taclonex Ointment and some other medicines can interact with each other. Especially tell your doctor if you use:

How should I use Taclonex Ointment?

Using Taclonex Ointment:

What are the possible side effects of Taclonex Ointment?

The most common side effects are:

 Other less common side effects with Taclonex Ointment include:

Taclonex Ointment may cause serious side effects if you use too much or use it for too long. Taclonex Ointment can pass through your skin. Serious side effects may include:

Your doctor may do special blood and urine tests to check your calcium levels and adrenal gland function while you are using Taclonex Ointment.

Call your doctor about any side effect that bothers you or that does not go away.

These are not all of the side effects with Taclonex Ointment. Ask your doctor or pharmacist for more information.

How should I store Taclonex Ointment?

General information about Taclonex Ointment

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Taclonex Ointment for a condition for which it was not prescribed. Do not give ointment to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Taclonex Ointment. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Taclonex Ointment that is written for health professionals.

Additional consumer information is available at (800) 521-8813.

What are the ingredients in Taclonex Ointment?

Active ingredients: calcipotriene hydrate, betamethasone dipropionate

Inactive ingredients: mineral oil, PPG-15 stearyl ether, dl-alpha tocopherol, white petrolatum.

Rx only

Manufactured by:LEO Laboratories Ltd. (LEO Pharma)Dublin, Ireland

Marketed by:Warner Chilcott (US), LLC Rockaway, NJ 07866 USA1-800-521-8813

U.S. Patent Nos.: RE39,706 E and 6,753,013.

3230G0253230G125022608-05

Revised July 2008

NDC 0430-3230-16 TACLONEX (calcipotriene 0.005% and betamethasone dipropionate 0.064%)  Ointment

Rx only

For Topical Use Only

Net Wt. 100 g

Each gram contains 52.18 mcg of calcipotriene hydrate (equivalent to 50 mcg of calcipotriene) and 0.643 mg of betamethasone dipropionate (equivalent to 0.5 mg of betamethasone) in an ointment base of mineral oil, PPG-15 stearyl ether, dl-alpha tocopherol and white petrolatum.

Store Taclonex Ointment between 20 - 25° C (68 - 77° F); excursions permitted between 15 - 30° C (59 - 86° F).

Keep out of reach of children.

Usual Dosage: Apply once daily, or as directed by physician. See Insert for complete information.

Manufacturer

Warner Chilcott (US), LLC

Active Ingredients

Source

• U.S. National Library of Medicine
• DailyMed
•  Last Updated: 2nd of March 2011