ZELSUVMI- berdazimer

ZELSUVMI is a nitric oxide releasing agent. The mechanism of action for the treatment of molluscum contagiosum is unknown. The pharmacodynamics of ZELSUVMI are unknown. Plasma hydrolyzed MAP3 (hMAP3), a structural marker for berdazimer, and nitrate levels were evaluated in n=34 subjects 2 to 12 years of age with MC. Subjects applied ZELSUVMI once-daily for two weeks to a total treatment area of 484 cm 2 There were no apparent differences in methemoglobin levels throughout the study.

ZELSUVMItrademark is indicated for the topical treatment of molluscum contagiosum (MC) in adults and pediatric patients 1 year of age and older. ZELSUVMItrademark is a nitric oxide (NO) releasing agent indicated for the topical treatment of molluscum contagiosum (MC) in adults and pediatric patients 1 year of age and older.

DOSAGE AND ADMINISTRATION
Dispense equal amounts from Tube A and Tube B per the dosing guide. 2 Mix together and immediately apply a thin layer of ZELSUVMI. 2 Apply once daily to each MC lesion for up to 12 weeks. 2 For topical use only and not for ophthalmic, oral, or intravaginal use. 2 ZELSUVMI is supplied in a carton containing the following: Tube A containing berdazimer gel Tube B containing hydrogel Dosing guide Mix together equal amounts of gel from Tube A and Tube B before application [see Dosage and Administration (2. 2) Do not premix or store mixed ZELSUVMI. Instruct the patient to refer to the ZELSUVMI “Instructions for Use” for detailed instructions on the preparation and administration of ZELSUVMI [see Instructions for Use] Dispense equal amounts (0. 5 mL) of gel from Tube A and Tube B on the dosing guide. Immediately put the caps back on Tube A and Tube B tightly. Mix together on the dosing guide. Immediately apply ZELSUVMI as an even thin layer. Apply ZELSUVMI once daily to each MC lesion for up to 12 weeks. Wash hands after applying ZELSUVMI, unless hands are being treated. Allow ZELSUVMI to dry for 10 minutes after application. Avoid application to uninvolved skin and avoid transfer of applied ZELSUVMI to other areas, including the eye. Avoid swimming, bathing, or washing for 1 hour after application of ZELSUVMI. ZELSUVMI is for topical use only and not for ophthalmic, oral, or intravaginal use.
Instructions For Use
IFU Page 1 IFU Step 1.

The most commonly reported adverse reactions (>=1%) are application site reactions, including pain (such as burning or stinging sensations, 18. 7%), erythema (11. 7%), pruritus (5. 7%), exfoliation (5. 0%), dermatitis (4. 9%), swelling (3. 5%), erosion (1. 6%), discoloration (1. 5%), vesicles (1. 5%), irritation (1. 2%), and infection (1. 1 To report SUSPECTED ADVERSE REACTIONS, contact LNHC, Inc. at 1-855-330-7546 or FDA at 1-800-FDA-1088 or www. gov/medwatch 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. In three double-blind, vehicle-controlled clinical trials (Trial 1, and Trial 2 and Trial 3, which were similarly designed to Trial 1), 1596 adult and pediatric subjects were treated with ZELSUVMI or vehicle gel topically once daily for up to 12 weeks [see Clinical Studies (14) Table 1: Adverse Reactions Reported by >= 1% of Subjects with MC Treated with ZELSUVMI (and Greater than Vehicle) Day 1 through Week 12 in Trials 1, 2, and 3 ZELSUVMI N=916 Vehicle Gel N=680 Adverse Reaction Mild n (%) Moderate n (%) Severe n (%) Mild n (%) Moderate n (%) Severe n (%) Subjects with any TEAE* 220 (24. 6) Application Site Paindagger 113 (12. 4) 0 Application Site Erythema 48 (5. 3) 0 Application Site Pruritus 36 (3. 3) 0 Application Site Exfoliation 18 (2. 2) 0 0 0 Application Site Dermatitis 16 (1. 3) 0 Application Site Swelling 17 (1. 1) 0 Pyrexia 14 (1. 1) 0 Application Site Erosion 7 (0. 1) 0 0 Application Site Discoloration 13 (1. 1) 0 0 Application Site Vesicles 5 (0. 0) 0 0 1 (0. 1) 0 Vomiting 5 (0. 1) 0 0 Application Site Irritation 7 (0. 4) 0 0 0 0 Upper Respiratory Tract Infection 6 (0. 1) 0 Application Site Infection 4 (0. 1) 0 * TEAE en dash treatment emergent adverse events.

Risk Summary There are no available data on ZELSUVMI use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of berdazimer to pregnant rats and rabbits increased malformations in the presence of severe maternal toxicity ( see Data The available data do not allow the calculation of relevant comparisons between the systemic exposure of berdazimer observed in animal studies and the systemic exposure that would be expected in humans after topical use of ZELSUVMI. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Systemic embryo-fetal development studies were conducted in rats and rabbits. In an embryofetal development study in rats, oral dose levels of 28, 95, or 189 mg/kg/day berdazimer were administered during the period of organogenesis. Maternal mortality and elevated methemoglobin levels were noted in dams receiving doses of 95 and 189 mg/kg/day. The maternal no observable adverse effect level (NOAEL) was 28 mg/kg/day. Fetal skeletal malformations (changes in the lumbar and thoracic centra or arches, missing thoracic arches and centra, additional bone in the thoracic arches, missing lumbar centra and arches, and fused ribs) and visceral malformations (cleft palate) and decreased fetal weights were observed in litters from dams receiving 189 mg/kg/day. The fetal NOAEL was 95 mg/kg/day. In an embryo-fetal development study in rabbits, oral dose levels of 47, 142, or 284 mg/kg/day berdazimer were administered during the period of organogenesis. Maternal mortality, aborted fetuses, adverse clinical observations, and elevated methemoglobin levels were noted in pregnant rabbits receiving doses of 142 and 284 mg/kg/day. The maternal NOAEL was 47 mg/kg/day. Decreased fetal weights were noted from pregnant rabbits receiving 284 mg/kg/day. The fetal NOAEL was 142 mg/kg/day. Risk Summary There are no data on the presence of berdazimer or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZELSUVMI and any potential adverse effects on the breastfed infant from ZELSUVMI or from the underlying maternal condition. The safety and effectiveness of ZELSUVMI for the topical treatment of MC have been established in pediatric patients 1 year of age and older. Use of ZELSUVMI for this indication is supported by data from three randomized, vehicle-controlled, double-blind trials involving 1596 subjects of which 1575 were pediatric subjects with MC (904 were exposed to ZELSUVMI; 29 subjects were less than 2 years of age, including one subject less than 1 year of age, and 875 were 2 to 17 years of age) [see Clinical Studies (14) The safety and effectiveness of ZELSUVMI have not been established in pediatric patients younger than 1 year of age. Of the total number of ZELSUVMI-treated subjects in clinical studies for MC, none were 65 to 74 years of age, and one was 75 years of age and older [see Clinical Studies (14).

NONCLINICAL TOXICOLOGY
The carcinogenic potential of berdazimer gel was assessed in a 2-year dermal mouse carcinogenicity study. There were no drug-related tumor findings associated with daily topical administration of berdazimer gel to mice at doses up to 4% berdazimer gel. Berdazimer was mutagenic in a bacterial mutagenicity assay (Ames assay) but was not clastogenic in an in vitro chromosomal aberration assay in human peripheral blood lymphocytes or in an in vivo micronucleus assay in rats. There were no berdazimer related effects on male or female fertility and early embryonic parameters in rats at oral doses up to 189 mg/kg/day.
CLINICAL STUDIES
The efficacy of ZELSUVMI was evaluated in 3 multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials in subjects with MC (Trials 1, 2, and 3; NCT04535531 NCT03927703 NCT03927716 In the three trials, 3% of subjects were less than 2 years of age and 96% of subjects were 2 to 17 years of age. The trial population included 51% male, 88% White, 6% Black, and 6% Other; for ethnicity, 21% of subjects identified as Hispanic/Latino, 78% as non-Hispanic/Latino, and 1% were not reported. Subjects had 3-70 baseline MC lesions. At baseline, the average MC lesion count was 20.2. The primary efficacy endpoint was the proportion of subjects achieving complete clearance at Week 12. Complete clearance was defined as the subject having a total MC lesion count of 0 at assessment. The key secondary efficacy endpoint was complete clearance rate at Week 8. Efficacy was demonstrated in Trials 1 and 2. The results are summarized in Table 2. Table 2: Complete Clearance Rate at Week 12 and Week 8 in Subjects with MC in Trials 1 and 2 Trial 1 Trial 2 ZELSUVMI (N=444) Vehicle (N=447) ZELSUVMI (N=237) Vehicle (N=118) Complete Clearance Rate at Week 12 (Primary Endpoint) 32.4% 19.7% 30.0% 20.3% Treatment Difference (95% Confidence Interval) 12.8% (7.1%, 18.6%) 9.2% Complete Clearance Rate at Week 8 (Secondary Endpoint) 19.6% 11.6% 13.9% 5.9% Treatment Difference (95% Confidence Interval) 7.5% 7.8% In Trial 3, the complete clearance rates at Week 12 were 26% versus 22% for ZELSUVMI and vehicle, respectively, with 95% confidence interval (-5%, 14%).
Patient Package Insert
PATIENT INFORMATION ZELSUVMItrademark (zel-SOOV-mee) (berdazimer) topical gel Important information: ZELSUVMI is for use on the skin (for topical use) only. What is ZELSUVMI? ZELSUVMI is a prescription medicine used on the skin (topical) to treat molluscum contagiosum (MC) in adults and children 1 year of age and older. It is not known if ZELSUVMI is safe and effective in children under 1 year of age. Before using ZELSUVMI, tell your healthcare provider about all your medical conditions, including if you: have other skin problems. are pregnant or plan to become pregnant. It is not known if ZELSUVMI will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if ZELSUVMI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with ZELSUVMI. Tell your healthcare provider about all the medicines you take How should I use ZELSUVMI? Read the Instructions for Use Use ZELSUVMI exactly as your healthcare provider tells you to use it. The ZELSUVMI carton contains: 1 tube that contains berdazimer gel (Tube A) 1 tube that contains hydrogel (Tube B) 1 Dosing Guide The gels contained in Tube A and Tube B must be mixed together on the Dosing Guide before you apply ZELSUVMI to your skin. Do not After mixing, apply an even, thin layer of ZELSUVMI right away to each MC bump. Apply ZELSUVMI 1 time each day. Do not Allow ZELSUVMI to dry for 10 minutes and do not Wash your hands after applying ZELSUVMI, unless your hands are being treated for MC. If someone else applies ZELSUVMI for you, they should wash their hands after applying ZELSUVMI. What are the possible side effects of ZELSUVMI? Application site reactions. Stop using ZELSUVMI The most common side effects of ZELSUVMI include: the following skin side effects at the application site: pain burning stinging redness itching peeling or flaking itchy, dry skin rash swelling breakdown of the outer layer of the skin (erosion) lightening or darkening of the skin blisters irritation infection These are not all of the possible side effects of ZELSUVMI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store ZELSUVMI? Store ZELSUVMI at room temperature between 68°F to 77°F (20°C to 25°C) in a dry location. Do not premix or store mixed ZELSUVMI. Product contains alcohol and should be kept away from open flame. Do not freeze ZELSUVMI. After use, immediately put caps back on Tube A (berdazimer gel) and Tube B (hydrogel) tightly. Throw away if not used within 60 days after receiving ZELSUVMI. General information about the safe and effective use of ZELSUVMI. What are the ingredients in ZELSUVMI? Tube A Active ingredient: Inactive ingredients: Tube B Inactive ingredients: Manufactured for: LNHC, Inc. Durham, NC 27703 U.S. Patents: www.pelthos.com/patents For more information, call 1-855-330-7546 or go to www.Zelsuvmi.com. This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 01/2024

LNHC, Inc.

ZELSUVMI- berdazimer Product manual source documgent