Taclonex

Taclonex® (calcipotriene and betamethasone dipropionate) Ointment contains calcipotriene hydrate and betamethasone dipropionate.

It is intended for topical use.

Calcipotriene hydrate is a synthetic vitamin D3 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
• C27H40O3,H2O, 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 C28H37FO7, 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® (calcipotriene and betamethasone dipropionate) 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® (calcipotriene and betamethasone dipropionate) Ointment (calcipotriene 0.005% and betamethasone dipropionate 0.064%) is available in 60 gram collapsible tubes (NDC 0430-3230-15).

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

Keep out of reach of children.

Manufactured by: LEO Laboratories Ltd. (LEO Pharma) Dublin, Ireland. FDA Rev date: 9/25/2007

This section provides information on the proper use of a number of products that contain betamethasone and calcipotriene. It may not be specific to Taclonex. Please read with care.

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

This medicine should only be used on the skin or scalp only. Do not get it in your eyes, nose, mouth, vagina, or apply it on your face, under your arms, or on your groin area. Do not use it on skin or scalp areas that have cuts or scrapes. If it does get on these areas, rinse it off right away with water.

This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

To help clear up your skin or scalp problem completely, it is very important that you keep using this medicine for the full time of treatment. Do not miss any doses.

This medicine should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other skin conditions, especially if you think that a skin infection may be present. This medicine should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

The treated areas should not be bandaged or covered after the medicine is applied.

To use the foam:

• Wash your hands before and after using this medicine.
• Shake the foam can before using the medicine.
• Apply the medicine to the affected areas of the skin and rub it in gently.
• Use this medicine within 6 months after opening.
• This medicine can catch on fire. Do not use it near heat, an open flame, or while smoking.

To use the ointment:

• Wash your hands with soap and water before and after using this medicine.
• Apply a thin layer to the affected areas of the skin and rub it in gently.
• Do not use the ointment for more than 8 weeks unless your doctor has told you to.

To use the topical suspension:

• Wash your hands with soap and water before and after using this medicine.
• Shake the bottle before using the medicine.
• Part your hair so you can see the patches on your scalp.
• Apply enough medicine to the affected areas on your scalp and rub it in gently.
• Do not wash your hair or take a bath or shower right after applying this medicine.
• Do not apply this medicine in the 12 hours before or after using any hair chemical treatments. Talk with your doctor first about it.
• Do not use the topical suspension for more than 8 weeks unless your doctor has told you to.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For topical dosage form (foam):
  • For plaque psoriasis:
    • Adults—Apply to the affected area of the skin once a day for up to 4 weeks or until the area is cleared or as determined by your doctor. Do not use more than 60 grams every 4 days.
    • Children—Use and dose must be determined by your doctor.
• For topical dosage form (ointment):
  • For plaque psoriasis:
    • Adults—Apply to the affected area of the skin once a day for up to 4 weeks or until the area is cleared or as determined by your doctor. Do not use more than 100 grams per week.
    • Children 12 to 17 years of age—Apply to the affected area of the skin once a day for up to 4 weeks or until the area is cleared or as determined by your doctor. Do not use more than 60 grams per week.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
• For topical dosage form (suspension):
  • For plaque psoriasis of the body:
    • Adults—Apply to the affected area of the skin once a day for up to 8 weeks or until the area is cleared or as determined by your doctor. Do not use more than 100 grams per week.
    • Children—Use and dose must be determined by your doctor.
  • For plaque psoriasis of the scalp:
    • Adults—Apply to the affected area on the scalp once a day for up to 8 weeks or until the area is cleared or as determined by your doctor. Do not use more than 100 grams per week.
    • Children 12 to 17 years of age—Apply to the affected area on the scalp once a day for up to 8 weeks or until the area is cleared or as determined by your doctor. Do not use more than 60 grams per week.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Keep the bottle of topical suspension in the carton when not in use. Use it within 6 months after it has been opened.

Store the foam can at room temperature, away from heat and direct light. Do not keep this medicine inside a car where it could be exposed to extreme heat. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood, urine, and other tests may be needed to check for unwanted effects.

If your psoriasis does not improve within a few weeks or become worse, check with your doctor.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. The risk is greater for children and patients who use large amounts for a long time. Talk to your doctor if you have more than one of these symptoms while you are using this medicine: darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

This medicine may cause too much calcium to build up in your body. Talk to your doctor if you have more than one of these symptoms while you are using this medicine: abdominal or stomach pain, confusion, constipation, depression, dry mouth, headache, incoherent speech, increased urination, loss of appetite, a metallic taste, muscle weakness, nausea, thirst, unusual tiredness, vomiting, or weight loss.

Check with your doctor right away if you have a blistering, burning, crusting, dryness, flaking, itching, scaling, severe redness, soreness, or swelling of the skin.

Make sure your doctor knows if you are also having ultraviolet (UV) light treatments (phototherapy) for your psoriasis before using this medicine.

This medicine may make your skin more sensitive to sunlight. Use a sunscreen and wear protective clothing when you are outdoors. Avoid sunlamps and tanning beds.

Do not use cosmetics or other skin care products on the treated areas.

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. Patients should wash their hands after applying Taclonex®Ointment. Therapy should be discontinued when control is achieved.

Patients 18 years and older should not use more than 100 g per week and patients 12 to 17 years should not use more than 60 g per week. Treatment of more than 30% body surface area is not recommended.

Taclonex® Ointment should not be used with occlusive dressings unless directed by a physician. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Taclonex® Ointment is not for oral, ophthalmic, or intravaginal use.

Topically applied Taclonex® Ointment can be absorbed in sufficient amounts to produce systemic effects [See Warnings and Precautions (5.1, 5.2)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

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/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 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.

A 104-week oral carcinogenicity study was conducted with calcipotriene in male and female rats at doses of 1, 5 and 15 mcg/kg/day (corresponding to dosages of approximately 6, 30, and 90 mcg/m2/day). Beginning week 71, the dosage for high-dose animals of both genders was reduced to 10 mcg/kg/day (corresponding to a dosage of approximately 60 mcg/m2/day). A treatment-related increase in benign C-cell adenomas was observed in the thyroid of females that received 15 mcg/kg/day. A treatment-related increase in benign pheochromocytomas was observed in the adrenal glands of males that received 15 mcg/kg/day. No other statistically significant differences in tumor incidence were observed when compared to control. The relevance of these findings to patients is unknown.

When betamethasone dipropionate was applied topically to CD-1 mice for up to 24 months at dosages approximating 1.3, 4.2 and 8.5 mcg/kg/day in females, and 1.3, 4.2, and 12.9 mcg/kg/day in males (corresponding to dosages of up to approximately 26 mcg/m2/day and 39 mcg/m2/day, in females and males, respectively), no significant changes in tumor incidence were observed when compared to control.

When betamethasone dipropionate was administered via oral gavage to male and female Sprague Dawley rats for up to 24 months at dosages of 20, 60, and 200 mcg/kg/day (corresponding to dosages of approximately 3, 10, and 30 mcg/m2/day), no significant changes in tumor incidence were observed when compared to control.

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/m2/day) of calcipotriene indicated no impairment of fertility or general reproductive performance. Studies in male rats at oral doses of up to 200 mcg/kg/day (1200 mcg/m2/day), and in female rats at oral doses of up to 1000 mcg/kg/day (6000 mcg/m2/day), of betamethasone dipropionate indicated no impairment of fertility.

Clinical Trials Conducted in Subjects 18 years and older with Plaque Psoriasis

In an international, multi-center, double-blind, vehicle- and active-controlled, parallel-group trial, 1603 subjects with mild to very severe plaque psoriasis on trunk and limbs were treated once daily for 4 weeks. Subjects 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 subjects was 48.4 years and 60.5% were male. Most subjects had disease of moderate severity at baseline.

Efficacy was assessed as the proportion of subjects 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 lesions(s) could just be felt. Table 3 contains the response rates for this trial.

Table 3

Percentage of Subjects with Absent or Very Mild Disease According to the Investigator's Global Assessment of Disease Severity at End of Treatment (4 weeks).*

*Subjects with mild disease at baseline were required to have "Absent" disease to be considered a success.


In addition to the pivotal trial (N = 490), four randomized, double-blind, vehicle- or active-controlled, parallel-group trials were conducted and provided supportive evidence of efficacy. These trials included a total of 1058 subjects treated with Taclonex® Ointment once daily for up to 4 weeks.

Clinical Trial Conducted in Subjects 12 to 17 years with Plaque Psoriasis

A prospective, uncontrolled trial (N=33) was conducted in pediatric subjects ages 12 to 17 years with plaque psoriasis involving 5-30% of the body surface area. Approximately 91% of subjects had moderate disease at baseline. Subjects were treated once daily for up to 4 weeks with Taclonex® Ointment. All subjects were evaluated for safety including calcium metabolism (N=33) and 32 subjects were evaluated for HPA axis suppression. [see Clinical Pharmacology (12.2)]

 See FDA-approved patient labeling (Patient Information)

Inform patients of the following:

• Instruct adult patients (18 years and older) not to use more than 100 g per week.
• Instruct pediatric patients (12 to 17 years) not to use more than 60 g per week.
• Discontinue therapy when control is achieved unless directed otherwise by the physician.
• Avoid use of Taclonex® Ointment on the face, underarms, groin or eyes. If this medicine gets on face or in eyes, wash area right away.
• Do not occlude the treatment area with a bandage or other covering unless directed by the physician.
• Note that local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids.
• Wash hands after application.
• Instruct patients not to use other products containing calcipotriene or a corticosteroid should not be used with Taclonex® Ointment without first talking to the physician.
• Instruct patients who use Taclonex® Ointment to avoid excessive exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc.).

Manufactured by:

LEO Laboratories Ltd. (LEO Pharma)

Dublin, Ireland

Distributed by:

LEO Pharma Inc.

Seven Giralda Farms,, Madison, New Jersey 07940 USA

1-877-494-4536

PATIENT INFORMATION

Taclonex® (TAK-lo-NEKS)
(calcipotriene and betamethasone dipropionate)

Ointment, 0.005%/0.064%

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

Important information: Taclonex® Ointment is for use on the skin only (topical use only). Do not use Taclonex® Ointment on the face, under arms or on groin area. Do not swallow Taclonex® Ointment. Another product, Taclonex® Topical Suspension contains the same medicine that is in Taclonex® Ointment and is used to treat plaque psoriasis on the scalp. If you use both medicines to treat your plaque psoriasis, be sure to follow your doctor’s directions carefully so that you do not use too much of one or both of these medications.

What is Taclonex® Ointment?
Taclonex® Ointment is a prescription medicine that is for use on the skin only (a topical medicine). Taclonex® Ointment is used to treat plaque psoriasis in patients 12 years of age and older.

Taclonex® Ointment has not been studied in patients under the age of 12 years.

Who should not use Taclonex® Ointment?

Do not use Taclonex® Ointment if you:

• have thin skin (atrophy) at the site to be treated
• are allergic to anything in Taclonex® Ointment. See the end of this leaflet for a complete list of ingredients.

What should I tell my doctor before using Taclonex® Ointment?

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

• have a skin infection. Your skin infection should be treated before starting Taclonex® Ointment.
• have a calcium metabolism disorder
• have one of the following types of psoriasis:
  • erythrodermic psoriasis
  • exfoliative psoriasis
  • pustular psoriasis
• are getting phototherapy treatments (light therapy) for your psoriasis
• are pregnant or planning to become pregnant. It is not known if Taclonex® Ointment can harm your unborn baby. You and your doctor will have to decide if Taclonex® Ointment is right for you while pregnant.
• are breastfeeding. It is not known if Taclonex® Ointment passes into your milk and if it can harm your baby.

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:

• other corticosteroid medicines
• other medicines for your psoriasis

How should I use Taclonex® Ointment?

• Use Taclonex® Ointment exactly as prescribed by your doctor.
• If you are 18 years of age or older, you should not use more than 100 grams of Taclonex® Ointment in 1 week.
• If you are 12 to 17 years of age, you should not use more than 60 grams of Taclonex® Ointment in 1 week.
• Apply Taclonex® Ointment once a day to the areas of your skin affected by psoriasis. Gently rub Taclonex® Ointment into your affected skin areas.
• Only use Taclonex® Ointment as directed by your doctor. Taclonex® Ointment is recommended for up to 4 weeks of treatment. Do not use Taclonex® Ointment for more than 4 weeks unless prescribed by your doctor.
• Do not use Taclonex® Ointment on the face, under arms or on groin area. If you accidentally get Taclonex® Ointment on the face or in the eyes wash the area with water right away.
• If you forget to use Taclonex® Ointment, use it as soon as you remember. Then go on as before.
• Wash your hands well after applying Taclonex® Ointment.

Using Taclonex® Ointment:
Do not bandage or tightly cover the treated skin area.

Remove the cap and check that the aluminum seal covers the tube before the first use. To break the seal, turn the cap over and punch through the seal.

What should I avoid while using Taclonex® Ointment?
Avoid spending a long time in the sunlight. Avoid tanning booths and sunlamps. Use sunscreen if you have to be in the sunlight. Talk to your doctor if you get a sunburn.

What are the possible side effects of Taclonex® Ointment?
The most common side effects are:

• itching
• rash

Other less common side effects with Taclonex® Ointment include:

• redness of the skin
• skin irritation
• skin burning
• inflamed hair pores (folliculitis)
• change of skin color (at the site of application)
• rash with pus-filled papules
• thinning of the skin (atrophy)
• swollen fine blood vessels (this makes your skin appear red at the site of application)

Taclonex® Ointment may cause serious side effects. Serious side effects are more likely to happen if you use too much Taclonex® Ointment, use it for too long, or use it with other topical medicines that contain corticosteroids, calcipotriene, or certain other ingredients. Check with your doctor before using other topical medicines. Taclonex® Ointment can pass through your skin. Serious side effects may include:

• too much calcium in your blood or urine
• adrenal gland problems

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?

• Store Taclonex® Ointment at room temperature, 68°F - 77°F (20°C - 25°C); Make sure the cap on the tube is tightly closed.
• Taclonex® Ointment has an expiration date (exp.) marked on the tube. Do not use the ointment after this date.
• Keep Taclonex® Ointment and all medicines out of the reach of children and pets.

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 Taclonex® 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.

What are the ingredients in Taclonex® Ointment?
Active ingredients: calcipotriene hydrate, betamethasone dipropionate.
Inactive ingredients: butylhydroxytoluene, mineral oil, polyoxypropylene stearyl ether, all-rac-alpha-tocopherol, white petrolatum.

Manufactured by:

LEO Laboratories Ltd. (LEO Pharma)

Dublin, Ireland

Distributed by:

LEO Pharma Inc.

Seven Giralda Farms, Madison, New Jersey  07940 USA

1-877-494-4536

Revised: 01/2017