Calcipotriene and Betamethasone Dipropionate: Package Insert and Label Information (Page 3 of 4)

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 (9, 30 and 90 mcg/m2 /day, respectively), no significant changes in tumor incidence were observed when compared to control.

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 (6, 30, and 90 mcg/m2 /day, respectively). Beginning week 71, the dosage for high-dose animals of both genders was reduced to 10 mcg/kg/day (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 (up to 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 (120, 360, and 1200 mcg/m2 /day, respectively), 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.

14 CLINICAL STUDIES

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: Calcipotriene and Betamethasone Dipropionate 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 lesion(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)*
Calcipotriene and Betamethasone Dipropionate Ointment Calcipotriene Betamethasone dipropionate Vehicle
N = 490 N = 480 N = 476 N = 157
*
Subjects with mild disease at baseline were required to have “Absent” disease to be considered a success.
Absent or very mild disease 48.0% 16.5% 26.3% 7.6%

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 Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate 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)].

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Calcipotriene and Betamethasone Dipropionate Ointment is off-white to yellow in color, available in collapsible tubes of:

60 gram (NDC 66993-938-61)
100 gram (NDC 66993-938-65)

16.2 Storage

Store Calcipotriene and Betamethasone Dipropionate Ointment between 20°C — 25°C (68°F — 77°F); excursions permitted between 15°C — 30°C (59°F — 86°F). [See USP controlled room temperature.]

16.3 Handling

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

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 Calcipotriene and Betamethasone Dipropionate 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.
  • Advise patients to report any visual symptoms to their healthcare providers.
  • Advise a woman to use Calcipotriene and Betamethasone Dipropionate Ointment on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise breastfeeding women not to apply Calcipotriene and Betamethasone Dipropionate Ointment directly to the nipple and areola to avoid direct infant exposure.
  • Instruct patients not to use other products containing calcipotriene or a corticosteroid should not be used with Calcipotriene and Betamethasone Dipropionate Ointment without first talking to the physician.
  • Instruct patients who use Calcipotriene and Betamethasone Dipropionate 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 12, Ireland

Distributed by:
Prasco Laboratories
Mason, OH 45040 USA

PATIENT INFORMATION Calcipotriene and Betamethasone Dipropionate Ointment, 0.005%/0.064%

Read the Patient Information that comes with Calcipotriene and Betamethasone Dipropionate 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: Calcipotriene and Betamethasone Dipropionate Ointment is for use on the skin only (topical use only). Do not use Calcipotriene and Betamethasone Dipropionate Ointment on the face, under arms or on groin area. Do not swallow Calcipotriene and Betamethasone Dipropionate Ointment. Another product, Calcipotriene and Betamethasone Dipropionate Topical Suspension contains the same medicine that is in Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment?

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

Calcipotriene and Betamethasone Dipropionate Ointment has not been studied in patients under the age of 12 years.

Who should not use Calcipotriene and Betamethasone Dipropionate Ointment?

Do not use Calcipotriene and Betamethasone Dipropionate Ointment if you:

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

What should I tell my doctor before using Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment can harm your unborn baby. You and your doctor will have to decide if Calcipotriene and Betamethasone Dipropionate Ointment is right for you while pregnant.
  • are breastfeeding or plan to breastfeed. It is not known if Calcipotriene and Betamethasone Dipropionate Ointment passes into your milk and if it can harm your baby. If you use Calcipotriene and Betamethasone Dipropionate Ointment while breastfeeding, use Calcipotriene and Betamethasone Dipropionate Ointment on the smallest area of skin and for the shortest time needed. If you use Calcipotriene and Betamethasone Dipropionate Ointment, do not apply Calcipotriene and Betamethasone Dipropionate Ointment to your nipple or areola to avoid getting Calcipotriene and Betamethasone Dipropionate Ointment into your baby’s mouth.

Tell your doctor about all the medicines you take, including prescription, and nonprescription medicines, vitamins and herbal supplements.

Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment?

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

Using Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment?

The most common side effects are:

  • itching
  • rash

Other less common side effects with Calcipotriene and Betamethasone Dipropionate 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)

Calcipotriene and Betamethasone Dipropionate Ointment may cause serious side effects. Serious side effects are more likely to happen if you use too much Calcipotriene and Betamethasone Dipropionate 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. Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment. Ask your doctor or pharmacist for more information.

Vision problems. Calcipotriene and Betamethasone Dipropionate Ointment may increase your chance of developing cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with Calcipotriene and Betamethasone Dipropionate Ointment.

How should I store Calcipotriene and Betamethasone Dipropionate Ointment?

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

General information about Calcipotriene and Betamethasone Dipropionate Ointment

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Calcipotriene and Betamethasone Dipropionate Ointment for a condition for which it was not prescribed. Do not give Calcipotriene and Betamethasone Dipropionate 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 Calcipotriene and Betamethasone Dipropionate Ointment. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Calcipotriene and Betamethasone Dipropionate Ointment that is written for health professionals.

What are the ingredients in Calcipotriene and Betamethasone Dipropionate 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 12, Ireland

Distributed by:
Prasco Laboratories
Mason, OH 45040 USA

Revised: 03/2020

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