Difamilast

Difamilast is an inhibitor of phosphodiesterase-4 (PDE-4). Difamilast’s inhibition of PDE-4 (a major cyclic adenosine monophosphate (AMP)-metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP and decreased productions of various cytokines and chemokines.

• & USAGE ADQUEY is indicated for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis. ADQUEY is a phosphodiesterase 4 inhibitor indicated for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis.ICD-10: L20.9

• None. None.contraindicated

DOSAGE & ADMINISTRATION ADQUEY is for topical use only and not for ophthalmic, oral, or intravaginal use. Apply a thin layer of ADQUEY twice daily to affected areas and rub in completely. Wash hands after application. Avoid areas of the skin that are infected when applying ADQUEY. For topical use only. Not for ophthalmic, oral, or intravaginal use. (2) Apply a thin layer of ADQUEY twice daily to affected areas and rub in completely. (2)

The most common adverse reaction occurring in ≥1% of subjects is nasopharyngitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc. at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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. The safety of ADQUEY was assessed in two double-blind, vehicle-controlled clinical trials (Trial 2 and Trial 3) that enrolled 532 adult and pediatric subjects 2 years of age and older in Japan with mild to moderate atopic dermatitis (AD). Subjects applied ADQUEY or vehicle ointment topically twice daily for 4 weeks [ see Clinical Studies (14) ]. Adverse reactions reported by ≥1% of ADQUEY-treated subjects and more frequently than in subjects receiving vehicle are listed in Table 1. Table 1: Adverse Reactions Occurring in ≥1% of Adult and Pediatric Subjects 2 Years of Age and Older Treated with ADQUEY for Mild to Moderate Atopic Dermatitis (and Greater than Vehicle) through Week 4 in Trials 2 and 3 Adverse Reaction ADQUEY (N=267) n (%) Vehicle (N=265) n (%) Nasopharyngitis 16(6) 10(4) Less common (<1%) adverse reactions in subjects treated with ADQUEY in Trials 2 and 3 included application site folliculitis, contact dermatitis, application site rash, and molluscum contagiosum.

8.1 Pregnancy Risk Summary The available data on the use of topical difamilast during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, difamilast administered subcutaneously to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 30 and 3 times the maximum recommended human dose (MRHD), respectively. Difamilast induced increased post-implantation loss, decreased fetal weight, retarded ossification and increased visceral abnormalities in rats at subcutaneous dose 263 times the MRHD. Difamilast induced increased skeletal variations in rabbits at subcutaneous doses 14 times the MRHD ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is 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% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats were dosed subcutaneously during the period of organogenesis with up to 100 mg/kg/day difamilast (263 times the MRHD based on AUC comparison).

Metabolism

Absorption The pharmacokinetics (PK) of ADQUEY were investigated in 31 pediatric subjects 2 years of age and older with moderate to severe atopic dermatitis and a mean ± SD body surface area (BSA) involvement of 44 ± 13% (range 25% to 80%). In this trial, subjects applied an average of approximately 4.3 g of ADQUEY ointment, 1% (dose range was 1.7 to 11.7 g per application) twice daily for 2 weeks.

• Feb 12, 2026NDANDA219474Acrotech Biopharma

1. 1Blister1100%
2. 2Chills1100%
3. 3Eczema Nummular1100%
4. 4Erythema1100%
5. 5Pruritus1100%
6. 6Rhinorrhoea1100%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Difamilast as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Phase 3 Trial of OPA-15406 Foam in Children and Infants With Atopic Dermatitis
  Not yet recruiting · Phase 3 · Interventional · 198 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT07184645updated 2025-09-22
• A Phase 3 Trial to Demonstrate the Superiority of 1% OPA-15406 Foam to the Vehicle in Adult Patients With Atopic Dermatitis
  Not yet recruiting · Phase 3 · Interventional · 156 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT07173478updated 2025-09-15
• To Demonstrate the Superiority of IMP (1% OPA-15406 Ointment) to the Vehicle in Adult Patients With AD
  Completed · Phase 3 · Interventional · 270 enrolled · Otsuka Beijing Research Institute
  NCT05667623updated 2025-08-29
• A Long-term Trial of OPA-15406 in Infants With Atopic Dermatitis
  Completed · Phase 3 · Interventional · 41 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT05372653updated 2025-03-30
• To Demonstrate the Superiority of IMP (0.3% and 1% OPA-15406 Ointment) Versus the Vehicle in Pediatric Patients with AD
  Completed · Phase 3 · Interventional · 240 enrolled · Otsuka Beijing Research Institute
  NCT05650320updated 2025-03-25
• This Study is to Assess the Efficacy of Difamilast Ointment in Mild to Moderate Atopic Dermatitis(AD)
  Completed · Phase 3 · Interventional · 153 enrolled · Acrotech Biopharma Inc.
  NCT05608343updated 2024-08-15
• A Open-label Study to Assess the Long-term Safety of Difamilast Ointment 1% in Mild to Moderate Atopic Dermatitis
  Completed · Phase 3 · Interventional · 542 enrolled · Acrotech Biopharma Inc.
  NCT05571943updated 2024-08-09
• A Study to Evaluate the Effectiveness and Safety of Topical OPA-15406 Ointment to Treat Participants With Atopic Dermatitis
  Completed · Phase 2 · Interventional · 121 enrolled · Otsuka Pharmaceutical Development & Commercialization, Inc.
  NCT02068352updated 2021-11-23
• Comparison Trial of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis
  Completed · Phase 3 · Interventional · 251 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT03911401updated 2021-01-25
• Comparison Trial of OPA-15406 Ointment in Adult Patients With Atopic DermatitisSyndrome
  Completed · Phase 3 · Interventional · 364 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT03908970updated 2021-01-25

Frequently asked questions

How does Difamilast work?

Difamilast is an inhibitor of phosphodiesterase-4 (PDE-4). Difamilast’s inhibition of PDE-4 (a major cyclic adenosine monophosphate (AMP)-metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP and decreased productions of various cytokines and chemokines.

What is Difamilast used for?

According to FDA labeling, Difamilast carries indications including: & USAGE ADQUEY is indicated for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis. ADQUEY is a phosphodiesterase 4 inhibitor indicated for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Difamilast?

Difamilast is classified as Phosphodiesterase 4 Inhibitors, Decreased Cytokine Production.

What are the brand names for Difamilast?

Difamilast is marketed under brand names including Adquey.

What are the contraindications for Difamilast?

Difamilast labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.