Calcipotriene, Betamethasone Dipropionate

Prescription

Tên thương mại: Calcipotriene and Betamethasone Dipropionate

Dạng bào chế

Topical

Đường dùng

TOPICAL

Nhà sản xuất

Bryant Ranch Prepack

About This Medication

11 DESCRIPTION Calcipotriene and Betamethasone Dipropionate Ointment, 0.005%/0.064% contains calcipotriene and betamethasone dipropionate. It is intended for topical use only. Calcipotriene is a synthetic vitamin D 3 analogue. Chemically, calcipotriene is (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1 (alpha),3(beta),24-triol, with the empirical formula C 27 H 40 O 3 , a molecular weight of 412.3, and the following structural formula: Calcipotriene 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 C 28 H 37 FO 7 , 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 50.00 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 mineral oil, PPG-15 stearyl ether, dl-alpha tocopherol and white petrolatum.

Hoạt chất

Thành phần	Hàm lượng
Betamethasone Dipropionate	-
Calcipotriene	-

Chỉ định & Cách dùng

1 INDICATIONS AND USAGE 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 is a vitamin D analogue and corticosteroid combination product indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older.

Cơ chế hoạt động

12.1 Mechanism of Action Calcipotriene and Betamethasone Dipropionate Ointment combines the pharmacological effects of calcipotriene as a synthetic vitamin D 3 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.

Liều dùng & Cách dùng

2 DOSAGE AND ADMINISTRATION 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. • Apply Calcipotriene and Betamethasone Dipropionate Ointment to affected area(s) once daily for up to 4 weeks. Discontinue therapy when control is achieved. (2) • Adult patients should not use more than 100 g per week. (2) • Patients ages 12 to 17 years should not use more than 60 g per week. (2) • Treatment of more than 30% body surface area is not recommended. (2) • Do not use with occlusive dressings unless directed by a physician. (2) • Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. (2) • Not for oral, ophthalmic, or intravaginal use. (2)

Side Effects Overview

6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥1%) are pruritus and scaly rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Clinical Trials Conducted in Subjects 18 years and older with Plaque Psoriasis The data described below reflect exposure to calcipotriene and betamethasone dipropionate ointment in 2448 subjects with plaque psoriasis, including 1992 exposed for 4 weeks, and 289 exposed for 8 weeks. Calcipotriene and betamethasone dipropionate ointment was studied primarily in placebo- and active-controlled trials (N = 1176, and N = 1272, respectively). The population was 15-97 years old, 61% males and 39% females, mostly white (97%) and had a baseline disease severity ranging from mild to very severe. Most subjects received once daily application, and the median weekly dose was 24.5 g. The percentage of subjects reporting at least one adverse event was 27.1% in the calcipotriene and betamethasone dipropionate ointment group, 33.0% in the calcipotriene group, 28.3% in the betamethasone group, and 33.4% in the vehicle group. Table 1 Adverse Events Reported by ≥1% of Subjects by Preferred Term Calcipotriene and betamethasone dipropionate ointment N = 2448 Calcipotriene N = 3197 Betamethasone dipropionate N = 1164 Vehicle N = 470 Any Adverse Event 663 (27.1) 1055 (33.0) 329 (28.3) 157 (33.4) Preferred Term # of subjects (%) Pruritus 75 (3.1) 183 (5.7) 38 (3.3) 43 (9.1) Headache 69 (2.8) 75 (2.3) 44 (3.8) 12 (2.6) Nasopharyngitis 56 (2.3) 77 (2.4) 34 (2.9) 9 (1.9) Psoriasis 30 (1.2) 47 (1.5) 14 (1.2) 5 (1.1) Rash scaly 30 (1.2) 40 (1.3) 0 (0.0) 1 (0.2) Influenza 23 (0.9) 34 (1.1) 14 (1.2) 6 (1.3) Upper respiratory tract infection 20 (0.8) 19 (0.6) 12 (1.0) 3 (0.6) Erythema 15 (0.6) 54 (1.7) 3 (0.3) 5 (1.1) Application site pruritus 13 (0.5) 24 (0.8) 10 (0.9) 6 (1.3) Skin irritation 11 (0.4) 60 (1.9) 8 (0.7) 5 (1.1) Pain 7 (0.3) 12 (0.4) 3 (0.3) 5 (1.1) Burning sensation 6 (0.2) 30 (0.9) 3 (0.3) 6 (1.3) A lesional/perilesional adverse event was generally defined as an adverse event located ≤ 2 cm from the lesional border. Table 2 Lesional/Perilesional Adverse Events Reported by ≥ 1% of Subjects Calcipotriene and betamethasone dipropionate ointment N = 2448 Calcipotriene N = 3197 Betamethasone dipropionate N = 1164 Vehicle N = 470 Any Adverse Event 213 (8.7) 419 (13.1) 85 (7.3) 76 (16.2) Preferred Term # of subjects (%) Pruritus 69 (2.8) 170 (5.3) 31 (2.7) 41 (8.7) Rash scaly 29 (1.2) 38 (1.2) 0 (0.0) 0 (0.0) Application site pruritus 12 (0.5) 24 (0.8) 10 (0.9) 6 (1.3) Erythema 9 (0.4) 36 (1.1) 2 (0.2) 4 (0.9) Skin irritation 9 (0.4) 51 (1.6) 8 (0.7) 5 (1.1) Burning sensation 6 (0.2) 25 (0.8) 3 (0.3) 5 (1.1) For subjects who reported lesional/perilesional adverse events, the median time to onset was 7 days for calcipotriene and betamethasone dipropionate ointment, 7 days for calcipotriene, 5 days for betamethasone dipropionate, and 3 days for vehicle. Other less common reactions (less than 1% but more than 0.1%) were, in decreasing order of incidence, folliculitis, rash papular, rash pustular, and skin hypopigmentation. Skin atrophy, telangiectasia and skin hyperpigmentation were reported infrequently (0.1%). In a separate trial, subjects (N = 207) with at least moderate disease severity were given calcipotriene and betamethasone dipropionate ointment intermittently on an “as needed” basis for up to 52 weeks. The median use was 15.4 g per week. The effects of calcipotriene and betamethasone dipropionate ointment on calcium metabolism were not studied and the effects on the HPA axis were not adequately studied. The following adverse reactions were reported by 1% or more of the subjects: pruritus (7.2%), psoriasis (3.4%), skin atrophy (1.9%), folliculitis (1.4%), burning sensation (1.4%), skin depigmentation (1.4%), ecchymosis (1.0%), erythema (1.0%) and hand dermatitis (1.0%). One case of serious flare-up of psoriasis was reported. 6.2 Postmarketing Experience 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.

Cảnh báo & Thận trọng

5 WARNINGS AND PRECAUTIONS • 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) 5.1 Hypercalcemia and Hypercalciuria 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)] . 5.2 Effects on Endocrine System 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. 5.3 Ophthalmic Adverse Reactions 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. 5.4 Allergic Contact Dermatitis with Topical Corticosteroids 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. 5.5 Allergic Contact Dermatitis with Topical Calcipotriene Allergic contact dermatitis has been observed with use of topical calcipotriene. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.6 Skin Irritation If irritation develops, treatment with Calcipotriene and Betamethasone Dipropionate Ointment should be discontinued and appropriate therapy instituted. 5.7 Risk of Ultraviolet Light Exposure 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.

Chống chỉ định

4 CONTRAINDICATIONS None. None.

Dược động học

12.3 Pharmacokinetics Absorption In Trial C described above, the systemic effect of calcipotriene and betamethasone dipropionate ointment in extensive plaque psoriasis was investigated. In this trial, 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 calcipotriene and betamethasone dipropionate ointment on the body in combination with calcipotriene and betamethasone dipropionate 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.

Frequently Asked Questions

1 INDICATIONS AND USAGE 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 is a vitamin D analogue and corticosteroid combination product indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older.

2 DOSAGE AND ADMINISTRATION 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 …

5 WARNINGS AND PRECAUTIONS • 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 …

4 CONTRAINDICATIONS None. None.

Calcipotriene, Betamethasone Dipropionate is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

References & Data Sources

• DailyMed — Calcipotriene, Betamethasone Dipropionate drug label (National Library of Medicine)
• openFDA — Calcipotriene, Betamethasone Dipropionate label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 388525 (NLM Normalized Drug Names)
• NDC Directory — Calcipotriene, Betamethasone Dipropionate (FDA National Drug Code)

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Nguồn dữ liệu: DailyMed (NLM), openFDA, MFDS