Sofpironium (Topical) (Monograph)

Brand name: SofdraTM
Drug class: Astringents

Introduction

Sofpironium, a quaternary ammonium analogue of glycopyrrolate, is an anticholinergic drug.

Uses for Sofpironium (Topical)

Primary Axillary Hyperhidrosis

Used topically for treatment of primary axillary hyperhidrosis in adults and pediatric patients ≥9 years of age.

Primary axillary hyperhidrosis causes excessive underarm sweating due to overactive eccrine glands. Treatment ranges from topical antiperspirants to botulinum toxin, oral anticholinergics, or surgery for severe cases.

Sofpironium (Topical) Dosage and Administration

General

Patient Monitoring

Monitor patients for lack of sweating when in hot or very warm environments.

Administration

Administer topically as a 12.45% gel.

Apply to clean, dry, unshaven underarms (do not shave within 8 hours or shower within 30 minutes prior). Dispense one pump onto the supplied applicator and apply to one underarm, spreading to cover entire underarm area; repeat with a separate pump for the other underarm. Allow to dry for 5 minutes before dressing.

Wash hands with soap immediately after use. Do not touch underarms after applying. Do not wash or shower for at least 8 hours after application.

Do not apply to broken skin or use with occlusive dressings.

Avoid contact with eyes. Avoid fires, flames, or smoking during and shortly after application.

Dosage

Dosage of sofpironium bromide is expressed in terms of sofpironium.

Pediatric Patients

Primary Axillary Hyperhidrosis

Topical

≥9 years of age: Apply one pump (72 mg) per underarm once daily at bedtime.

Do not exceed one application per day.

Adults

Primary Axillary Hyperhidrosis

Topical

Apply one pump (72 mg) per underarm once daily at bedtime.

Do not exceed one application per day.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Cautions for Sofpironium (Topical)

Contraindications

Patients with conditions worsened by anticholinergic effects, such as glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe or complicating ulcerative colitis, toxic megacolon, myasthenia gravis, and Sjögren’s syndrome.

Warnings/Precautions

Urinary Retention

Use with caution in patients with history of urinary retention, particularly those with prostatic hypertrophy or bladder-neck obstruction.

Discontinue use and consult a healthcare provider if urinary retention symptoms occur.

Control of Body Temperature

May impair sweating and increase risk of heat-related illness in high temperatures.

Discontinue use and avoid in hot environments if reduced or absent sweating occurs.

Operating Machinery or an Automobile

May cause transient blurred vision. If this occurs, discontinue use and avoid activities requiring clear vision until symptoms resolve.

Specific Populations

Pregnancy

No human pregnancy data available; animal studies showed no harm, but human risk unknown.

Lactation

No human lactation data available; sofpironium appeared in rat milk when administered as a sub-Q dose. Weigh benefits of breastfeeding against maternal need for the drug and potential infant risk.

Pediatric Use

Safety and effectiveness established in children ≥9 years of age; not evaluated in younger pediatric patients.

Geriatric Use

Few patients ≥65 years of age were studied; use with caution due to possible organ decline, comorbidities, and other drugs.

Hepatic Impairment

Not studied.

Renal Impairment

Not studied.

Common Adverse Effects

Most common adverse reactions (incidence ≥2%): dry mouth, blurred vision, mydriasis, urinary retention, application site pain, erythema, dermatitis, pruritus, and irritation.

Drug Interactions

Metabolized by CYP2D6 and CYP3A4. Inhibits CYP2D6, CYP3A4, organic cation transporter (OCT)1 and OCT2, and multidrug and toxin extrusion protein (MATE)1, but does not induce CYP1A2, CYP2B6, or CYP3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Coadministration with paroxetine, a strong CYP2D6 inhibitor, increased peak plasma concentrations and AUC of sofpironium by 2-fold. Avoid concomitant use of sofpironium with strong CYP2D6 inhibitors.

No clinically significant changes in pharmacokinetics observed when sofpironium was used concomitantly with CYP3A4 inhibitors.

Drugs Affecting or Affected by Transport Proteins

No clinically significant changes in pharmacokinetics observed when sofpironium was used with inhibitors of OCT2, MATE1, or MATE2-K.

Anticholinergic Drugs

Concomitant use may result in additive anticholinergic effects; avoid concomitant use.

Sofpironium (Topical) Pharmacokinetics

Absorption

Plasma Concentration

Mean time to peak plasma concentrations in adults: 5.34.

Mean time to peak plasma concentration in pediatrics: 4 hours.

Special Populations

Not studied in pregnant patients or those with renal or hepatic impairment.

Distribution

Protein Binding

Sofpironium: 34.8–37.8%.

Major metabolite BBI-4010: 2.3–3.7%.

Elimination

Metabolism

Primarily metabolized through nonenzymatic hydrolysis, CYP2D6 and CYP3A4 oxidative pathways, and glycine conjugation. In plasma, sofpironium is major component (38%) followed by the BB1-4010 metabolite (20%).

Elimination Route

Urinary excretion: <0.5% for both sofpironium and metabolite, BBI-4010.

Stability

Storage

Topical

Gel

Store upright at 20–25°C; excursions between 15–30°C permitted.

Keep away from heat or flame, as the product is flammable.

Actions

Quaternary ammonium analogue of the anticholinergic agent glycopyrrolate.
Blocks M3 muscarinic receptors on sweat glands, preventing acetylcholine activation and reducing sweat production.

Advice to Patients

Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Instruct patients to be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder). Instruct patients to discontinue use and consult a healthcare provider immediately should any of these signs or symptoms develop.
Advise patients that in the presence of high ambient temperature, heat illness due to decreased sweating can occur. Advise patients to watch for generalized lack of sweating when in hot or very warm environmental temperatures and to avoid using sofpironium if not sweating under these conditions.
Advise patients that transient blurred vision may occur with sofpironium. If this occurs, instruct patients to contact their healthcare provider, discontinue use of sofpironium, and avoid operating a motor vehicle or other machinery or performing hazardous work until symptoms resolve.
Advise patients to not shave armpits at least 8 hours before applying sofpironium.
Advise patients to not shower at least 30 minutes before applying sofpironium.
Advise patients to apply 1 pump actuation per underarm to clean, dry skin once a day at bedtime (total 2 pumps). Allow to dry completely (5 minutes) before putting on clothing. Instruct patients to wash their hands with soap and water immediately after applying sofpironium.
Advise patients to wait at least 8 hours after applying the gel to shower or wash underarms.
Instruct patients not to apply sofpironium to other body areas or to broken skin and to avoid using the topical gel with occlusive dressings.
Advise patients that sofpironium is flammable; avoid fire, flame, and smoking during and immediately following application.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Sofpironium is available through designated specialty pharmacies. Contact the manufacturer or consult the sofpironium website ([Web]) for specific availability information.