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.
A 104-week oral carcinogenicity study was conducted with calcipotriene in male and female rats at doses of 1, 5 and 15 mcg/kg/day (corresponding to dosages of approximately 6, 30, and 90 mcg/m2 /day). Beginning week 71, the dosage for high-dose animals of both genders was reduced to 10 mcg/kg/day (corresponding to a dosage of approximately 60 mcg/m2 /day). A treatment-related increase in benign C-cell adenomas was observed in the thyroid of females that received 15 mcg/kg/day. A treatment-related increase in benign pheochromocytomas was observed in the adrenal glands of males that received 15 mcg/kg/day. No other statistically significant differences in tumor incidence were observed when compared to control. The relevance of these findings to patients is unknown.
When betamethasone dipropionate was applied topically to CD-1 mice for up to 24 months at dosages approximating 1.3, 4.2, and 8.5 mcg/kg/day in females, and 1.3, 4.2, and 12.9 mcg/kg/day in males (corresponding to dosages of up to approximately 26 mcg/m2 /day and 39 mcg/m2 /day, in females and males, respectively), no significant changes in tumor incidence were observed when compared to control.
When betamethasone dipropionate was administered via oral gavage to male and female Sprague Dawley rats for up to 24 months at dosages of 20, 60, and 200 mcg/kg/day (corresponding to dosages of approximately 120, 360, and 1200 mcg/m2 /day), no significant changes in tumor incidence were observed when compared to control.
Calcipotriene did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, the human lymphocyte chromosome aberration test, or the mouse micronucleus test. Betamethasone dipropionate did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, or in the rat micronucleus test.
Studies in rats with oral doses of up to 54 mcg/kg/day (324 mcg/m2 /day) of calcipotriene indicated no impairment of fertility or general reproductive performance. Studies in male rats at oral doses of up to 200 mcg/kg/day (1200 mcg/m2 /day), and in female rats at oral doses of up to 1000 mcg/kg/day (6000 mcg/m2 /day), of betamethasone dipropionate indicated no impairment of fertility.
The safety and efficacy of WYNZORA Cream were evaluated in a randomized, multicenter, vehicle and active-comparator controlled, clinical trial (NCT03308799) in adult subjects with mild to moderate plaque psoriasis. In the trial, 794 subjects were randomized to 1 of 3 treatment groups: WYNZORA Cream, vehicle cream, or calcipotriene/betamethasone dipropionate topical suspension, 0.005%/0.064%. The majority of subjects in the trial (81.7%) had disease of moderate severity at baseline, while 18.3% of subjects had disease of mild severity. Disease severity was determined by a 5-grade Physician’s Global Assessment (PGA) scale.
The primary efficacy endpoint was the proportion of subjects with treatment success at Week 8. Treatment success was defined as at least a 2-grade improvement from baseline in the PGA score and an PGA score equating to “clear” or “almost clear”. Other evaluated outcomes included reduction in itch as defined by at least a 4-point improvement in the 11-point peak pruritus numeric rating scale (NRS) from baseline to Week 4. Table 2 presents the primary efficacy results.
|WYNZORA Cream(N=342)||Vehicle Cream(N=115)|
|PGA of Clear or Almost Clear And ≥2-grade Improvement||37.4%||3.7%|
|Difference from Vehicle (95% CI)||33.7%(27.4%, 40.0%)|
WYNZORA Cream was non-inferior to calcipotriene/betamethasone dipropionate topical suspension, 0.005%/0.064% for the primary endpoint of treatment success at Week 8 [Difference (95% CI): 14.6% (7.6%, 21.6%)].
Among subjects who had at least a peak pruritus NRS score of 4 at baseline, there was a higher percentage of subjects that achieved at least a 4-point improvement from baseline on the peak pruritus NRS score at Week 4 in the WYNZORA Cream group compared to the vehicle cream group (60.3% vs. 21.4%).
WYNZORA® (calcipotriene and betamethasone dipropionate) Cream, 0.005%/0.064%, is a white cream. Each gram of cream contains 50 mcg of anhydrous calcipotriene and 0.644 mg of betamethasone dipropionate. It is available as 60 g tubes individually packaged (NDC 73499-001-01).
Store 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.]
Do not freeze. Protect from light and excessive heat.
Unused product should be discarded six months after the tube has been opened.
Advise the patient to read the FDA-approved patient labeling (Patient Information).
- Instruct patients not to use more than 100 grams per week.
- Instruct patients to discontinue therapy when control is achieved unless directed otherwise by the healthcare provider.
- Advise patients to avoid use of WYNZORA Cream on the face, underarms, groin or eyes.
- Advise patients not to occlude the treatment area with a bandage or other covering unless directed by the healthcare provider.
- Instruct patients to wash hands after application.
Local Reactions and Skin Atrophy
Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids.
Hypercalcemia and Hypercalciuria
Advise patients that hypercalcemia and hypercalciuria may occur with the use of WYNZORA Cream [see Warnings and Precautions (5.1)].
HPA Axis Suppression, Cushing’s Syndrome, and Hyperglycemia
Advise patients that WYNZORA Cream can cause HPA access suppression, Cushing’s syndrome, and/or hyperglycemia [see Warnings and Precautions (5.2)].
Ophthalmic Adverse Reactions
Advise patients to avoid contact of WYNZORA Cream with eyes and to report any visual symptoms [see Warnings and Precautions (5.5)].
Possible Avoidance of Other Products Containing Calcipotriene or a Corticosteroid
Instruct patients not to use other products containing calcipotriene or a corticosteroid with WYNZORA Cream without first talking to the healthcare provider.
Pregnancy and Lactation
- Advise pregnant women that WYNZORA Cream may increase the potential risk of having a low birth weight infant and to use WYNZORA Cream on the smallest area of skin and for the shortest duration possible [see Use in Specific Populations (8.1)].
- Advise breastfeeding women not to apply WYNZORA Cream directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2)].
MC2 Therapeutics, Ltd. Leatherhead, KT22 7EP, United Kingdom
Distributed by:EPI Health, LLC. Charleston, SC 29403, USA
|This Patient Information has been approved by the U.S. Food and Drug Administration||Issued: 11/2020|
|PATIENT INFORMATIONWYNZORA® (win-ZOR-uh)(calcipotriene and betamethasone dipropionate)Cream|
|Important information: WYNZORA® Cream is for use on the skin only (topical use only). Do not get WYNZORA® Cream near or in your mouth, eyes, or vagina.|
|There are other medicines that contain the same medicine that is in WYNZORA® Cream and are used to treat plaque psoriasis. Do not use other products containing calcipotriene or a corticosteroid medicine with WYNZORA® Cream without talking to your healthcare provider first.|
|What is WYNZORA® Cream?WYNZORA® Cream is a prescription medicine used on the skin (topical) to treat plaque psoriasis in people 18 years of age and older.It is not known if WYNZORA® Cream is safe and effective in children under 18 years of age.|
|Before using WYNZORA® Cream, tell your healthcare provider about all of your medical conditions, including if you: |
| How should I use WYNZORA® Cream? |
| What are the possible side effects of WYNZORA® Cream?WYNZORA® Cream may cause serious side effects, including: |
| || |
| How should I store WYNZORA® Cream? |
|General information about WYNZORA® CreamMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use WYNZORA® Cream for a condition for which it was not prescribed. Do not give WYNZORA® Cream to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about WYNZORA® Cream that is written for health professionals.|
|What are the ingredients in WYNZORA® Cream?Active ingredients: calcipotriene and betamethasone dipropionateInactive ingredients: isopropyl myristate, mineral oil, medium-chain triglycerides, isopropyl alcohol, polyoxyl lauryl ether, poloxamer (407), polyoxyl 40 hydrogenated castor oil, carbomer interpolymer (type A), butylated hydroxyanisole, trolamine, dibasic sodium phosphate, heptahydrate, monobasic sodium phosphate, monohydrate, alpha-tocopherol and purified water.Manufactured for: MC2 Therapeutics, Ltd. Leatherhead, KT22 7EP, United Kingdom.Distributed by: EPI Health, LLC. Charleston, SC 29403, USA.For more information, go to www.wynzora.com or call 1–800-644-8240|
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