Sofdra

1 INDICATIONS AND USAGE SOFDRA is indicated for the treatment of primary axillary hyperhidrosis in adults and pediatric patients 9 years of age and older. SOFDRA is an anticholinergic indicated for the treatment of primary axillary hyperhidrosis in adults and pediatric patients 9 years of age and older ( 1 ).

2 DOSAGE AND ADMINISTRATION Do not shave armpits at least 8 hours before applying SOFDRA. Do not shower at least 30 minutes before applying SOFDRA. Apply SOFDRA to clean, dry skin once a day at bedtime. Apply a single pump actuation to the top of the supplied applicator. Spread the entire amount to cover 1 underarm. Apply a separate, single pump actuation to the top of the supplied applicator. Apply the entire amount to the second underarm. Allow to dry completely (5 minutes) before putting on clothing. Wash hands immediately with soap. For topical use only. Avoid fire, flame, and smoking during and immediately following application. Do not shower or wash underarms for at least 8 hours after application. Do not touch underarms after applying SOFDRA. Do not use more than once daily. Avoid transfer of SOFDRA to the periocular area [see Warnings and Precautions (5.3) ] . Do not apply SOFDRA to broken skin. Avoid using SOFDRA with occlusive dressings. Apply 1 pump of SOFDRA per underarm once a day at bedtime. For topical use only ( 2 ).

4 CONTRAINDICATIONS SOFDRA is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of sofpironium bromide (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjögren's syndrome). Medical conditions that can be exacerbated by the anticholinergic effect of SOFDRA (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjögren's syndrome) ( 4 ).

5 WARNINGS AND PRECAUTIONS Urinary Retention: Use with caution in patients with a history or presence of documented urinary retention. Discontinue use immediately and consult a healthcare provider should any signs or symptoms of urinary retention develop ( 5.1 ). Control of Body Temperature: Watch for generalized lack of sweating when in hot or very warm environmental temperatures and avoid using SOFDRA if not sweating under these conditions ( 5.2 ). Operating Machinery or an Automobile: Transient blurred vision may occur with use of SOFDRA. If blurred vision occurs, discontinue use and avoid operating a motor vehicle or other machinery until symptoms resolve ( 5.3 ). 5.1 Urinary Retention Use SOFDRA with caution in patients with a history or presence of documented urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder), especially in patients with prostatic hypertrophy or bladder-neck obstruction. Discontinue use immediately and consult a healthcare provider should any of these signs or symptoms develop. 5.2 Control of Body Temperature In the presence of high ambient temperature, heat illness (hyperpyrexia and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs, including SOFDRA. Watch for generalized lack of sweating when in hot or very warm environmental temperatures and avoid using SOFDRA if not sweating under these conditions. 5.3 Operating Machinery or an Automobile Transient blurred vision may occur with use of SOFDRA. If blurred vision occurs, discontinue use and avoid engaging in activities that require clear vision, such as operating a motor vehicle or other machinery or performing hazardous work, until the symptoms have resolved.

7 DRUG INTERACTIONS Anticholinergics: Coadministration of SOFDRA with anticholinergic medications may result in additive interaction leading to an increase in anticholinergic adverse effects. Avoid coadministration of SOFDRA with other anticholinergic-containing drugs ( 7.1 ). Strong Inhibitors of CYP2D6: Avoid co-administration of SOFDRA with drugs that are strong inhibitors of CYP2D6 ( 7.2 ). 7.1 Anticholinergics Coadministration of SOFDRA with anticholinergic medications may result in additive interaction leading to an increase in anticholinergic adverse effects [See Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] . Avoid coadministration of SOFDRA with other anticholinergic-containing drugs. 7.2 Strong Inhibitors of CYP2D6 Avoid co-administration of SOFDRA with drugs that are strong inhibitors of CYP2D6.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Urinary Retention [See Warnings and Precautions (5.1) ]. Most common adverse reactions (incidence ≥2%) are dry mouth, vision blurred, application site pain, application site erythema, mydriasis, application site dermatitis, application site pruritus, urinary retention, and application site irritation ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Botanix SB Inc. at 1-866-763-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 two double-blind, vehicle controlled clinical trials (CARDIGAN 1 and CARDIGAN 2) of 700 subjects 10 to 76 years of age (353 subjects treated with SOFDRA and 347 subjects treated with vehicle), 44% of subjects were male, 79% were White, 21% were Black, and 1% were Asian. A total of 618 subjects completed at least 6 weeks of treatment, including 307 subjects treated with SOFDRA and 311 subjects treated with vehicle. Table 1 summarizes the most frequent adverse reactions (≥2%) in subjects with primary axillary hyperhidrosis treated with SOFDRA. Table 1: Adverse Reactions Occurring in ≥2% of Subjects with Primary Axillary Hyperhidrosis Treated with SOFDRA in Trials CARDIGAN 1 and 2 Adverse Reactions SOFDRA (N = 353) n (%) Vehicle (N = 347) n (%) Note: COVID-19 was observed in 8 (2%) SOFDRA and 2 (0.6%) vehicle subjects. Dry mouth 51 (14%) 2 (0.6%) Vision blurred 30 (9%) 1 (0.3%) Mydriasis 23 (7%) 0 Urinary retention 8 (2%) 0 Table 2 shows the local skin reactions reported ≥2%, which occurred more commonly in the SOFDRA group. Table 2: Local Skin Reactions Reported in ≥2% of Subjects with Primary Axillary Hyperhidrosis Treated with SOFDRA in Trials CARDIGAN 1 and 2 Local Skin Adverse Reactions SOFDRA (N = 353) n (%) Vehicle (N = 347) n (%) Pain 29 (8%) 6 (2%) Erythema 23 (7%) 1 (0.3%) Dermatitis 21 (6%) 1 (0.3%) Pruritus 16 (5%) 2 (0.6%) Irritation 8 (2%) 1 (0.3%) Exfoliation 7 (2%) 1 (0.3%) In an open-label, long-term safety trial (ARGYLE), 197 subjects were treated for 48 weeks with SOFDRA. Adverse reactions occurring at a frequency ≥2% were vision blurred (19%), dry mouth (17%), application site pruritus (15%), application site pain (15%), application site dermatitis (11%), application site erythema (8%), application site irritation (6%), mydriasis (5%), application site rash (4%), upper respiratory tract infection (4%), dry eye (4%), urinary retention (4%), application site exfoliation (3%), application site folliculitis (3%), hypertension (3%), application site dryness (2%), viral upper respiratory tract infection (2%), influenza (2%), and headache (2%).

8.1 Pregnancy Risk Summary There are no available data with SOFDRA use in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneous administration of sofpironium bromide to pregnant rats and rabbits during the period of organogenesis resulted in no significant adverse effects at doses 31 and 10 times, respectively, the maximum recommended human dose (MRHD) ( see Data ). The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryofetal development study in rats, sofpironium bromide was not associated with embryofetal lethality or fetal malformations at subcutaneous dose levels of 1, 3, and 10 mg/kg/day administered during the period of organogenesis. The maternal and fetal survival, growth and development no observed adverse effect level (NOAEL) was 10 mg/kg/day (31 times the MRHD based on AUC comparisons). In an embryofetal development study in rabbits, sofpironium bromide was administered by subcutaneous injection to pregnant rabbits at doses of 0.4, 2 and 10 mg/kg/day during the period of organogenesis. Maternal toxicity as evidenced by decreased maternal body weight gain and feed consumption was observed in all sofpironium bromide treated groups. The decrease in maternal body weight was considered severe at 10 mg/kg/day and was associated with embryofetal lethality. The maternal toxicity NOAEL could not be established in the study. The NOAEL for embryo-fetal development toxicity was 2 mg/kg/day (10 times the MRHD based on AUC comparison). Fetal malformation was not observed with sofpironium bromide treatment at doses up to 10 mg/kg/day (57 times the MRHD based on AUC comparison) in rabbits. In a pre- and postnatal development study, sofpironium bromide was administered by subcutaneous injection to pregnant rats at doses of 1, 3 and 6 mg/kg/day beginning on gestation day 6 through lactation day 20. Maternal toxicity associated with a 17% decrease in body weight gain noted at 6 mg/kg/day (approximately 19 times the MRHD based on AUC comparisons) when compared to the control group. No sofpironium bromide-related effects on prenatal and postnatal development, neurobehavioral or reproductive performance of offspring were noted at doses up to 6 mg/kg/day (approximately 19 times the MRHD based on AUC comparison).