Phosphodiesterase 4 Inhibitor

Zoryve

Approved 15 Dec 2023TopicalFoam

The FDA lists this product in 4 strengths and forms.

Indications

ZORYVE topical foam, 0.3%, is a phosphodiesterase 4 inhibitor indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. ( 1.1 ) plaque psoriasis of the scalp and body in adult and pediatric patients 12 years of age and older. ( 1.2 )

1.1Seborrheic Dermatitis

ZORYVE ® topical foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older.

1.2Plaque Psoriasis

ZORYVE topical foam, 0.3%, is indicated for the treatment of plaque psoriasis of the scalp and body in adult and pediatric patients 12 years of age and older.

Contraindications

ZORYVE foam, 0.3%, is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C) [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . Moderate to severe liver impairment (Child-Pugh B or C). ( 4 )

Warnings and precautions

Flammability : The propellants in ZORYVE foam, 0.3%, are flammable. Avoid fire, flame, and smoking during and immediately following application. ( 5.1 )

5.1Flammability

The propellants in ZORYVE foam, 0.3%, are flammable. Avoid fire, flame, and smoking during and immediately following application.

Interactions

Co-administration of roflumilast with systemic CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously may increase roflumilast systemic exposure and may result in increased adverse reactions. If these products are co-administered with ZORYVE foam, 0.3%, weigh the potential for increased adverse reactions against benefit. ( 7.1 ) Co-administration of roflumilast with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased adverse reactions.

Indications

1.1Seborrheic Dermatitis

ZORYVE ® topical foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older.

1.2Plaque Psoriasis

ZORYVE topical foam, 0.3%, is indicated for the treatment of plaque psoriasis of the scalp and body in adult and pediatric patients 12 years of age and older.

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are insufficient data available on the use of ZORYVE foam, 0.3%, in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, roflumilast administered orally to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 21 and 18 times the maximum recommended human dose (MRHD), respectively.

Roflumilast induced post-implantation loss in rats at oral doses greater than or equal to 7 times the MRHD. Roflumilast induced stillbirth and decreased pup viability in mice at oral doses 11 and 34 times the MRHD, respectively. Roflumilast has been shown to adversely affect pup post-natal development when dams were treated with an oral dose 34 times the MRHD during pregnancy and lactation periods in mice (see Data ) .

The background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Clinical Considerations Labor and delivery Avoid using ZORYVE foam, 0.3%, during labor and delivery. There are no human studies that have investigated effects of ZORYVE foam, 0.3%, on preterm labor or labor at term; however, animal studies showed that oral roflumilast disrupted the labor and delivery process in mice.

Data Animal data In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast (21 times the MRHD on a mg/m 2 basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast did not affect embryo-fetal development at a maternal oral dose of 0.2 mg/kg/day (2 times the MRHD on a mg/m 2 basis). In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast for 10 weeks and females for 2 weeks prior to pairing and throughout the organogenesis period.

Roflumilast induced pre- and post-implantation loss at maternal oral doses greater than or equal to 0.6 mg/kg/day (7 times the MRHD on a mg/m 2 basis). Roflumilast did not cause fetal structural abnormalities at maternal oral doses up to 1.8 mg/kg/day (20 times the MRHD on a mg/m 2 basis). In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast during the period of organogenesis.

Roflumilast did not cause fetal structural abnormalities at the maternal oral doses of 0.8 mg/kg/day (18 times the MRHD on a mg/m 2 basis). In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast during the period of organogenesis and lactation. Roflumilast induced stillbirth and decreased pup viability at maternal oral doses greater than 2 mg/kg/day and 6 mg/kg/day, respectively (11 and 34 times the MRHD on a mg/m 2 basis, respectively).

Roflumilast induced delivery retardation in pregnant mice at maternal oral doses greater than 2 mg/kg/day (11 times the MRHD on a mg/m 2 basis). Roflumilast decreased pup rearing frequencies at a maternal oral dose of 6 mg/kg/day during pregnancy and lactation (34 times the MRHD on a mg/m 2 basis). Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at a maternal oral dose of 12 mg/kg/day (68 times the MRHD on a mg/m 2 basis).

Adverse reactions

The most common adverse reactions (reported in ≥ 1% of patients) are: Seborrheic dermatitis : nasopharyngitis, nausea, and headache. ( 6.1 ) Plaque psoriasis of the scalp and body : headache, diarrhea, nausea, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Arcutis Biotherapeutics, Inc. at 1-844-692-6729 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Seborrheic Dermatitis In two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 203 and STRATUM), 683 adult and pediatric subjects 9 years of age or older with seborrheic dermatitis were treated with ZORYVE foam, 0.3%, or vehicle foam once daily for 8 weeks [see Clinical Studies (14.1) ].

Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE foam, 0.3%. Table 1: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 9 Years of Age and Older with Seborrheic Dermatitis Treated with ZORYVE Foam, 0.3%, for 8 Weeks in Trial 203 and Trial STRATUM Adverse Reaction ZORYVE foam, 0.3% (N=458) n (%) Vehicle foam (N=225) n (%) Nasopharyngitis 7 (1.5) 1 (0.4) Nausea 6 (1.3) 0 (0) Headache 5 (1.1) 0 (0) The following additional adverse reactions were reported in fewer than 1% of subjects treated with ZORYVE foam, 0.3%: diarrhea and insomnia.

The adverse reaction profile in pediatric subjects was consistent with that observed in adults [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) ] . In 408 subjects who continued treatment with ZORYVE foam, 0.3%, for up to 24 to 52 weeks in an open-label, long-term trial, the adverse reaction profile was consistent with that observed in vehicle-controlled trials. Plaque Psoriasis In two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 204 and ARRECTOR), 734 adult and pediatric subjects 12 years of age and older with plaque psoriasis of the scalp and body were treated with ZORYVE foam, 0.3%, or vehicle foam once daily for 8 weeks [see Clinical Studies (14.2) ].

Table 2 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE foam, 0.3%. Table 2: Adverse Reactions Reported in ≥1% of Adult and Pediatric Subjects 12 Years of Age and Older with Plaque Psoriasis of the Scalp and Body Treated with ZORYVE Foam, 0.3%, for 8 Weeks in Trial 204 and Trial ARRECTOR Adverse Reaction ZORYVE foam, 0.3% (N=479) n (%) Vehicle foam (N=255) n (%) Headache 15 (3.1) 3 (1.2) Diarrhea 12 (2.5) 4 (1.6) Nausea 8 (1.7) 0 (0) Nasopharyngitis 6 (1.3) 2 (0.8) The following additional adverse reaction was reported in fewer than 1% of subjects treated with ZORYVE foam, 0.3%: insomnia.

The adverse reaction profile in pediatric subjects was consistent with that observed in adults [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) ] .

Zoryve

Indications

1.1Seborrheic Dermatitis

1.2Plaque Psoriasis

Contraindications

Warnings and precautions

5.1Flammability

Interactions

Two medicines in one question?

Zoryve

Indications

1.1Seborrheic Dermatitis

1.2Plaque Psoriasis

Contraindications

Warnings and precautions

5.1Flammability

Interactions

Two medicines in one question?

7.1Effects of Other Drugs on

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information

At a glance