Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

ZORYVE (NDA-217242)

(ROFLUMILAST)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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05/22/2025 (SUPPL-5)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revision underlined:

…

Seborrheic Dermatitis

…

Table 1: Adverse Reactions Reported in greater than or equal to 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

Please refer to label to view Table 1.

…

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)].

…

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 greater than or equal to 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

Please refer to label to view Table 2.

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)].

7 Drug Interactions

7.1 Effects of Other Drugs on ZORYVE Foam, 0.3%

Additions and/or revisions underlined:

Drugs that Inhibit Cytochrome P450 (CYP) Enzymes

No formal drug-drug interaction studies were conducted with ZORYVE foam, 0.3%; however, the co-administration of oral 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 [see Clinical Pharmacology (12.3)].

Oral Contraceptives Containing Gestodene and Ethinyl Estradiol

The co-administration of roflumilast with oral contraceptives containing gestodene and ethinyl estradiol 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 [see Clinical Pharmacology (12.3)].

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

…

Plaque Psoriasis

The safety and effectiveness of ZORYVE topical foam, 0.3%, for the treatment of plaque psoriasis of the scalp and body have been established in pediatric patients 12 years of age and older. Use of ZORYVE foam, 0.3%, in this age group is supported by data from two 8-week, vehicle-controlled trials which included 12 subjects 12 to 17 years of age, of whom 8 received ZORYVE foam, 0.3%. Use of ZORYVE foam, 0.3%, in pediatric patients 12 years of age and older is also supported by data from an open-label trial of 8 weeks duration which included 7 subjects 12 to 17 years of age treated with ZORYVE foam, 0.3%.

The safety and effectiveness of ZORYVE foam, 0.3%, in pediatric patients below the age of 12 years with plaque psoriasis have not been established.

8.5 Geriatric Use

Additions and/or revisions underlined:

…

Plaque Psoriasis

Of the 734 subjects with plaque psoriasis of the scalp and body exposed to ZORYVE foam, 0.3%, or vehicle for up to 8 weeks in the controlled clinical trials, 82 (11%) were 65 years of age or older, and 21 (3%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

8.1 Pregnancy

Additions and/or revisions underlined:

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).

…

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/m2 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/m2 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/m2 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/m2 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 fetalstructural abnormalities at the maternal oral doses of 0.8 mg/kg/day (18 times the MRHD on a mg/m2 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/m2 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/m2 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/m2 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/m2 basis).

8.2 Lactation

Additions and/or revisions underlined:

…

Data

Animal data

Roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively. The concentration of roflumilast in animal milk does not necessarily predict the concentration of drug in human milk.

8.3 Fertility

New subsection added:

In a human spermatogenesis study, oral roflumilast 500 mcg had no effects on semen parameters or reproductive hormones during the 3-month treatment period and the following 3-month off-treatment period.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Administration Instructions

Advise patients or caregivers that ZORYVE foam, 0.3%, is for topical use only and is not for ophthalmic, oral, or intravaginal use [see Dosage and Administration (2)].

Instruct patients or caregivers to shake the can of ZORYVE foam, 0.3%, prior to each use [see Dosage and Administration (2)].

Instruct patients or caregivers to wash hands after applying ZORYVE foam, 0.3% [see Dosage and Administration (2)].

…

PATIENT INFORMATION

Additions and/or revisions underlined:

…

What is ZORYVE foam?

ZORYVE foam is a prescription medicine used on the skin (topical) to treat:

seborrheic dermatitis in adults and children 9 years of age and older.
It is not known if ZORYVE foam is safe and effective in children with seborrheic dermatitis under 9 years of age.
plaque psoriasis of the scalp and body in adults and children 12 years of age and older.
It is not known if ZORYVE foam is safe and effective in children with plaque psoriasis of the scalp and body under 12 years of age.
…
How should I use ZORYVE foam?

Use ZORYVE foam exactly as your healthcare provider tells you to use it. See the “Instructions for Use” provided with this leaflet for directions about how to apply ZORYVE foam.
Shake the can of ZORYVE foam before each use.
…
What are the possible side effects of ZORYVE foam?
…
The most common side effects of ZORYVE foam in people treated for plaque psoriasis include:

headache
diarrhea
nausea
common cold
…