These Highlights Do Not Include All The Information Needed To Use Calcipotriene And Betamethasone Dipropionate Ointment Safely And Effectively. See Full Prescribing Information For Calcipotriene And Betamethasone Dipropionate Ointment.

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

Ointment, 0.005%/0.064%

Each gram of 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 off-white to yellow paraffin ointment base.

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.]

Topically applied Calcipotriene and Betamethasone Dipropionate Ointment can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1, 5.2)].

Keep out of reach of children.

Calcipotriene and Betamethasone Dipropionate Ointment, 0.005%/0.064% contains calcipotriene hydrate and betamethasone dipropionate. It is intended for topical use only.

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(alpha),3(beta),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(beta), 17,21-trihydroxy-16(beta)-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 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 off-white to yellow paraffin ointment base of butylhydroxytoluene, mineral oil, polyoxypropylene stearyl ether, all-rac-alpha-tocopherol, and white petrolatum.

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)

Safety and effectiveness of the use of Calcipotriene and Betamethasone Dipropionate Ointment in pediatric patients under the age of 12 years have not been established.

The safety and effectiveness of Calcipotriene and Betamethasone Dipropionate Ointment for the treatment of plaque psoriasis have been established in the age group 12 to 17 years. In a prospective, uncontrolled trial, 33 pediatric subjects ages 12-17 years with plaque psoriasis on the body were treated with Calcipotriene and Betamethasone Dipropionate Ointment for 4 weeks up to a maximum of 55.8 g per week. Subjects were assessed for HPA axis suppression and effects on calcium metabolism. No adverse effects on adrenal suppression were observed. No hypercalcemia was observed but one subject had a possible treatment-related increase in urinary calcium [see Clinical Pharmacology (12.2)].

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity when treated with topical drugs. They are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency upon the use of topical corticosteroids [see Warnings and Precautions (5.2)].

Rare systemic toxicities such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including striae have also been reported with use of topical corticosteroids in pediatric patients.

Of the total number of subjects in the clinical studies of Calcipotriene and Betamethasone Dipropionate Ointment, approximately 14% were 65 years and older and approximately 3% were 75 years and over.

No overall differences in safety or effectiveness of Calcipotriene and Betamethasone Dipropionate 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. However, greater sensitivity of some older individuals cannot be ruled out.

None.

If irritation develops, treatment with Calcipotriene and Betamethasone Dipropionate Ointment should be discontinued and appropriate therapy instituted.

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.

Calcipotriene and Betamethasone Dipropionate Ointment is indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older.

Calcipotriene and Betamethasone Dipropionate Ointment combines the pharmacological effects of calcipotriene hydrate as a synthetic vitamin D₃ analogue and betamethasone dipropionate as a synthetic corticosteroid. However, while their pharmacologic and clinical effects are known, the exact mechanisms of their actions in plaque psoriasis are unknown.

• Hypercalcemia and hypercalciuria have been observed. If either occurs, discontinue treatment until parameters of calcium metabolism normalize. (5.1)
• Calcipotriene and Betamethasone Dipropionate Ointment can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency during and after withdrawal of treatment. Risk factors include the use of high-potency topical corticosteroid, use over a large surface area or to areas under occlusion, prolonged use, concomitant use of more than one corticosteroid-containing product, altered skin barrier, liver failure, and use in pediatric patients. Modify use should HPA axis suppression develop. (5.2, 8.4)
• Calcipotriene and Betamethasone Dipropionate Ointment may increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. (5.3)

Apply an adequate layer of Calcipotriene and Betamethasone Dipropionate Ointment to the affected area(s) once daily for up to 4 weeks. Calcipotriene and Betamethasone Dipropionate Ointment should be rubbed in gently and completely. Patients should wash their hands after applying Calcipotriene and Betamethasone Dipropionate 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.

Calcipotriene and Betamethasone Dipropionate 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. Calcipotriene and Betamethasone Dipropionate Ointment is not for oral, ophthalmic, or intravaginal use.

Ointment, 0.005%/0.064% (3)

The following adverse reactions associated with the use of Calcipotriene and Betamethasone Dipropionate Ointment have been identified post-approval: pustular psoriasis and rebound effect.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Postmarketing reports for local adverse reactions to topical corticosteroids may also include: striae, dryness, acneiform eruptions, perioral dermatitis, secondary infection and miliaria.

Calcipotriene and Betamethasone Dipropionate Ointment can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of treatment. Factors that predispose a patient to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, concomitant use of more than one corticosteroid-containing product, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the cosyntropin stimulation test [see Clinical Pharmacology (12.2)].

In a trial evaluating the effects of Calcipotriene and Betamethasone Dipropionate Topical Suspension and Calcipotriene and Betamethasone Dipropionate Ointment on the HPA axis, 32 adult subjects were treated with Calcipotriene and Betamethasone Dipropionate Topical Suspension on the scalp and Calcipotriene and Betamethasone Dipropionate Ointment on the body. Adrenal suppression was identified in 5 of 32 subjects (15.6%) after 4 weeks of treatment [see Clinical Pharmacology (12.2)]. The effects of Calcipotriene and Betamethasone Dipropionate Ointment on the HPA axis following treatment durations of longer than 4 weeks have not been adequately studied.

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid.

Cushing's syndrome and hyperglycemia may also occur due to the systemic effects of topical corticosteroids. These complications are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids.

Pediatric patients may be more susceptible to systemic toxicity due to their higher skin surface to body mass ratios [see Use in Specific Populations (8.4), Clinical Pharmacology (12.2)].

Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.

Use of topical corticosteroids, including Calcipotriene and Betamethasone Dipropionate Ointment, may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products.

Avoid contact of Calcipotriene and Betamethasone Dipropionate Ointment with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

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.).

Hypercalcemia and hypercalciuria have been observed with use of Calcipotriene and Betamethasone Dipropionate Ointment. If hypercalcemia or hypercalciuria develops, treatment should be discontinued until parameters of calcium metabolism have normalized. In the trials that included assessment of the effects of Calcipotriene and Betamethasone Dipropionate Ointment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Calcipotriene and Betamethasone Dipropionate Ointment on calcium metabolism following treatment durations of longer than 4 weeks have not been evaluated [see Clinical Pharmacology (12.2)].

Patients who apply Calcipotriene and Betamethasone Dipropionate Ointment to exposed skin 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 Calcipotriene and Betamethasone Dipropionate Ointment.

NDC 66993-938-61

Rx only

PRASCO

Calcipotriene 0.005% and

Betamethasone Dipropionate 0.064%

Ointment

For Topical Use Only

Net Wt. 60 g

NDC 66993-938-65

Rx only

PRASCO

Calcipotriene 0.005% and

Betamethasone Dipropionate 0.064%

Ointment

For Topical Use Only

Net Wt. 100 g

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.

Allergic contact dermatitis has been observed with use of topical calcipotriene. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.

Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.

Ointment, 0.005%/0.064%

Each gram of 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 off-white to yellow paraffin ointment base.

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.]

Topically applied Calcipotriene and Betamethasone Dipropionate Ointment can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1, 5.2)].

Keep out of reach of children.

Calcipotriene and Betamethasone Dipropionate Ointment, 0.005%/0.064% contains calcipotriene hydrate and betamethasone dipropionate. It is intended for topical use only.

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(alpha),3(beta),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(beta), 17,21-trihydroxy-16(beta)-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 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 off-white to yellow paraffin ointment base of butylhydroxytoluene, mineral oil, polyoxypropylene stearyl ether, all-rac-alpha-tocopherol, and white petrolatum.

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)

Safety and effectiveness of the use of Calcipotriene and Betamethasone Dipropionate Ointment in pediatric patients under the age of 12 years have not been established.

The safety and effectiveness of Calcipotriene and Betamethasone Dipropionate Ointment for the treatment of plaque psoriasis have been established in the age group 12 to 17 years. In a prospective, uncontrolled trial, 33 pediatric subjects ages 12-17 years with plaque psoriasis on the body were treated with Calcipotriene and Betamethasone Dipropionate Ointment for 4 weeks up to a maximum of 55.8 g per week. Subjects were assessed for HPA axis suppression and effects on calcium metabolism. No adverse effects on adrenal suppression were observed. No hypercalcemia was observed but one subject had a possible treatment-related increase in urinary calcium [see Clinical Pharmacology (12.2)].

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity when treated with topical drugs. They are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency upon the use of topical corticosteroids [see Warnings and Precautions (5.2)].

Rare systemic toxicities such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including striae have also been reported with use of topical corticosteroids in pediatric patients.

Of the total number of subjects in the clinical studies of Calcipotriene and Betamethasone Dipropionate Ointment, approximately 14% were 65 years and older and approximately 3% were 75 years and over.

No overall differences in safety or effectiveness of Calcipotriene and Betamethasone Dipropionate 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. However, greater sensitivity of some older individuals cannot be ruled out.

None.

If irritation develops, treatment with Calcipotriene and Betamethasone Dipropionate Ointment should be discontinued and appropriate therapy instituted.

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.

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

Calcipotriene and Betamethasone Dipropionate Ointment is indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older.

Calcipotriene and Betamethasone Dipropionate Ointment combines the pharmacological effects of calcipotriene hydrate as a synthetic vitamin D₃ analogue and betamethasone dipropionate as a synthetic corticosteroid. However, while their pharmacologic and clinical effects are known, the exact mechanisms of their actions in plaque psoriasis are unknown.

• Hypercalcemia and hypercalciuria have been observed. If either occurs, discontinue treatment until parameters of calcium metabolism normalize. (5.1)
• Calcipotriene and Betamethasone Dipropionate Ointment can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency during and after withdrawal of treatment. Risk factors include the use of high-potency topical corticosteroid, use over a large surface area or to areas under occlusion, prolonged use, concomitant use of more than one corticosteroid-containing product, altered skin barrier, liver failure, and use in pediatric patients. Modify use should HPA axis suppression develop. (5.2, 8.4)
• Calcipotriene and Betamethasone Dipropionate Ointment may increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. (5.3)

Apply an adequate layer of Calcipotriene and Betamethasone Dipropionate Ointment to the affected area(s) once daily for up to 4 weeks. Calcipotriene and Betamethasone Dipropionate Ointment should be rubbed in gently and completely. Patients should wash their hands after applying Calcipotriene and Betamethasone Dipropionate 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.

Calcipotriene and Betamethasone Dipropionate 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. Calcipotriene and Betamethasone Dipropionate Ointment is not for oral, ophthalmic, or intravaginal use.

Ointment, 0.005%/0.064% (3)

The following adverse reactions associated with the use of Calcipotriene and Betamethasone Dipropionate Ointment have been identified post-approval: pustular psoriasis and rebound effect.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Postmarketing reports for local adverse reactions to topical corticosteroids may also include: striae, dryness, acneiform eruptions, perioral dermatitis, secondary infection and miliaria.

Calcipotriene and Betamethasone Dipropionate Ointment can cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of treatment. Factors that predispose a patient to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, concomitant use of more than one corticosteroid-containing product, use of occlusive dressings, altered skin barrier, liver failure, and young age. Evaluation for HPA axis suppression may be done by using the cosyntropin stimulation test [see Clinical Pharmacology (12.2)].

In a trial evaluating the effects of Calcipotriene and Betamethasone Dipropionate Topical Suspension and Calcipotriene and Betamethasone Dipropionate Ointment on the HPA axis, 32 adult subjects were treated with Calcipotriene and Betamethasone Dipropionate Topical Suspension on the scalp and Calcipotriene and Betamethasone Dipropionate Ointment on the body. Adrenal suppression was identified in 5 of 32 subjects (15.6%) after 4 weeks of treatment [see Clinical Pharmacology (12.2)]. The effects of Calcipotriene and Betamethasone Dipropionate Ointment on the HPA axis following treatment durations of longer than 4 weeks have not been adequately studied.

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid.

Cushing's syndrome and hyperglycemia may also occur due to the systemic effects of topical corticosteroids. These complications are rare and generally occur after prolonged exposure to excessively large doses, especially of high-potency topical corticosteroids.

Pediatric patients may be more susceptible to systemic toxicity due to their higher skin surface to body mass ratios [see Use in Specific Populations (8.4), Clinical Pharmacology (12.2)].

Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.

Use of topical corticosteroids, including Calcipotriene and Betamethasone Dipropionate Ointment, may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products.

Avoid contact of Calcipotriene and Betamethasone Dipropionate Ointment with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

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.).

Hypercalcemia and hypercalciuria have been observed with use of Calcipotriene and Betamethasone Dipropionate Ointment. If hypercalcemia or hypercalciuria develops, treatment should be discontinued until parameters of calcium metabolism have normalized. In the trials that included assessment of the effects of Calcipotriene and Betamethasone Dipropionate Ointment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Calcipotriene and Betamethasone Dipropionate Ointment on calcium metabolism following treatment durations of longer than 4 weeks have not been evaluated [see Clinical Pharmacology (12.2)].

Patients who apply Calcipotriene and Betamethasone Dipropionate Ointment to exposed skin 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 Calcipotriene and Betamethasone Dipropionate Ointment.

NDC 66993-938-61

Rx only

PRASCO

Calcipotriene 0.005% and

Betamethasone Dipropionate 0.064%

Ointment

For Topical Use Only

Net Wt. 60 g

NDC 66993-938-65

Rx only

PRASCO

Calcipotriene 0.005% and

Betamethasone Dipropionate 0.064%

Ointment

For Topical Use Only

Net Wt. 100 g

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.

Allergic contact dermatitis has been observed with use of topical calcipotriene. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.

Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.