Taclonex (Page 3 of 4)

12.3 Pharmacokinetics

Absorption

The systemic effect of Taclonex® Ointment in extensive psoriasis was investigated in the study described above. In this study, the serum levels of calcipotriene and betamethasone dipropionate and their major metabolites were measured after 4 weeks (maximum recommended duration of treatment) and also after 8 weeks of once daily application of Taclonex® Ointment on the body in combination with Taclonex Scalp® Topical Suspension on the scalp. Both calcipotriene and betamethasone dipropionate were below the lower limit of quantification in all serum samples of the 34 subjects evaluated. However, one major metabolite of calcipotriene (MC1080) was quantifiable in 10 of 34 (29.4%) subjects at week 4 and in five of 12 (41.7%) subjects at week 8. The major metabolite of betamethasone dipropionate, betamethasone 17-propionate (B17P) was also quantifiable in 19 of 34 (55.9%) subjects at week 4 and seven of 12 (58.3%) subjects at week 8. The serum concentrations for MC1080 ranged from 20-75 pg/mL. The clinical significance of this finding is unknown.

Metabolism

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

Calcipotriene is metabolized to MC1046 (the alpha,beta-unsaturated ketone analogue of calcipotriene), which is metabolized further to MC1080 (a saturated ketone analogue). MC1080 is the major metabolite in plasma. MC1080 is slowly metabolized to calcitroic acid.

Betamethasone dipropionate:
Betamethasone dipropionate is metabolized to betamethasone 17-propionate and betamethasone, including the 6beta-hydroxy derivatives of those compounds by hydrolysis. Betamethasone 17-propionate (B17P) is the primary metabolite.

13 NONCLINICAL TOXICOLOGY

13.1 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.

Long-term animal studies have not been performed to evaluate 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/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.

14 CLINICAL STUDIES

14.1 Controlled Clinical Studies

In an international, multi-center, double-blind, vehicle- and active-controlled, parallel-group study, 1603 subjects with mild to very severe psoriasis vulgaris 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). *

Taclonex® OintmentN = 490CalcipotrieneN = 480Betamethasone dipropionateN = 476VehicleN = 157
Absent or very mild disease48.0%16.5%26.3%7.6%

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 1058 subjects treated with Taclonex® Ointment once daily for up to 4 weeks.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Taclonex® Ointment is available in collapsible tubes of:

60 gram (NDC 54868-5680-0)

16.2 Storage

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

16.3 Handling

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

[See FDA-Approved Patient Labeling (17.5) ]

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.

17.1 Instructions for Use

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. This medication should not be used for any disorder other than that for which it has been prescribed. The treated skin area should not be bandaged or otherwise covered as to be occlusive, unless directed by the physician.

17.2 Adverse Reactions

Patients should report any signs of adverse reactions to their physician.

17.3 Concomitant Use of Other Corticosteroids

Other products containing calcipotriene or a corticosteroid should not be used with Taclonex® Ointment without first talking to the physician.

17.4 Excessive Exposure to Light

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 who use Taclonex® Ointment.

17.5 FDA-Approved Patient Labeling

Patient Information
Taclonex ® Ointment (pronounced TAK-lo-NEKS)
(calcipotriene 0.005% and betamethasone dipropionate 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 Scalp® Topical Suspension contains the same medicine that is in Taclonex® Ointment and is used to treat psoriasis vulgaris on the scalp. If you use both medicines to treat your psoriasis vulgaris, 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 psoriasis vulgaris in adults 18 years of age and older.
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:
have a calcium metabolism disorder
have one of the following types of psoriasis:
o erythrodermic psoriasis
o exfoliative psoriasis
o pustular psoriasis
• have severe kidney or liver disease
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 thin-skin (atrophy) at the site to be treated. You should not use Taclonex® Ointment.
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.
• Do not use more than the maximum recommended weekly amount of 100 grams of Taclonex® Ointment.
• 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 between 68 — 77° F (20 — 25° C); excursions permitted between 59 — 86° F (15 — 30° 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: mineral oil, PPG-15 stearyl ether, dl-alpha tocopherol, white petrolatum.

logologo
Manufactured by:
LEO Laboratories Ltd. (LEO Pharma)
Dublin, Ireland
Distributed by:
LEO Pharma Inc.
1 Sylvan Way, Parsippany, NJ 07054 USA
1-877-494-4536
U.S. Patent Nos.: RE39,706 E and 6,753,013.
024598-01
024599-01
Revised: 11/2010
logologo

Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, Oklahoma 74146

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