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.

CUTIVATE (NDA-019957)

(FLUTICASONE PROPIONATE)

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

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03/19/2021 (SUPPL-13)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Local Adverse Reactions

(Additions and/or revisions underlined)

The following local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximate decreasing order of occurrence: irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, hypertrichosis, and miliaria.

5.5 Ophthalmic Adverse Reactions

(Newly added subsection)

Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported postmarketing with the use of topical corticosteroids.

Avoid contact of CUTIVATE® Ointment with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following local adverse reactions have been identified during post-approval use of CUTIVATE® Ointment: acneiform dermatitis, edema, rash, hypoaesthesia, pustular psoriasis, skin atrophy.

The following systemic adverse reactions have been identified during post-approval use of CUTIVATE® Cream and CUTIVATE® Ointment: immunosuppression/Pneumocystis jirovecii pneumonia/leukopenia/thrombocytopenia; hyperglycemia/glycosuria; Cushing syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling).

The following local adverse reactions have been reported with the use of topical corticosteroids: telangiectasia, striae, dryness, folliculitis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria.

Ophthalmic adverse reactions including cataracts, glaucoma and increased intraocular pressure have been reported with the use of topical corticosteroids.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

There are no available data on CUTIVATE® Ointment use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Observational studies suggest an increased risk of low birthweight infants with the use of greater than 300 grams of potent or very potent topical corticosteroids during pregnancy (see Data). Advise pregnant women that CUTIVATE® Ointment may increase the risk of having a low birthweight infant and to use CUTIVATE® Ointment on the smallest area of skin and for the shortest duration possible.

In animal reproduction studies, subcutaneous administration of fluticasone propionate to pregnant mice, rats, and rabbits during organogenesis caused malformations characteristic of corticosteroids in each species (see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposure of fluticasone propionate observed in animal studies to the systemic exposure that would be expected in humans after topical use of CUTIVATE® Ointment.

The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or 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

Human Data

Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of potent or very potent topical corticosteroids exceeded 300 grams during the entire pregnancy, maternal use was associated with an increased risk of low birth weight infants.

Animal Data

In embryo-fetal development studies, pregnant rabbits, rats, and mice received subcutaneous doses of fluticasone propionate during organogenesis at doses up to 4, 100, and 150 µg/kg/day, respectively. A malformation characteristic of corticosteroids (cleft palate) was noted at the high dose in each species. Additional adverse effects were noted in rats and rabbits. Decreased fetal weights and retarded skeletal ossification were noted in rabbits at 4 µg/kg/day and rats at 100

µg/kg/day. Maternal toxicity and omphalocele were also noted in rats at 100 µg/kg/day. No malformations or developmental toxicity was noted in rabbits at 0.57 µg/kg/day, in rats at 10 µg/kg/day, or in mice at 15 µg/kg/day. Fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 ?g/kg tritiated fluticasone propionate to pregnant rats.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of fluticasone propionate in human milk, its effects on the breastfed infant, or its effects on milk production. It is not known whether topical administration of CUTIVATE® Ointment could result in sufficient systemic absorption to produce detectable quantities in human milk (see Clinical Considerations).

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CUTIVATE® Ointment and any potential adverse effects on the breastfed child from CUTIVATE® Ointment or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use CUTIVATE® Ointment on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply CUTIVATE® Ointment directly to the nipple and areola prior to breastfeeding to avoid direct infant exposure [see Use in Specific Populations (8.4)].

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Patient Information). Advise the patient:

Avoid contact with the eyes.
Do not bandage the treated skin area, or cover or wrap it to cause occlusion unless directed by the healthcare provider.
Report any signs of local adverse reaction to their healthcare provider.
Do not use on the face, underarms, or groin areas unless directed by the healthcare provider.
Advise a woman to use CUTIVATE® Ointment on the smallest area of skin and for the shortest duration possible while pregnant or breastfeeding. Advise breastfeeding women not to apply CUTIVATE® Ointment directly to the nipple and areola to avoid direct infant exposure.

PATIENT INFORMATION

(Additions and/or revisions underlined)

…

Before using CUTIVATE® Ointment, tell your healthcare provider about all of your medical conditions, including if you:

have an allergy to any of the ingredients in CUTIVATE® Ointment
have a skin infection at the site to be treated. You may also need medicine to treat the skin infection.
have adrenal gland problems
have liver problems
have diabetes
have thinning skin (atrophy) at the site to be treated
have cataracts or glaucoma
are pregnant or plan to become pregnant. It is not known if CUTIVATE® Ointment will harm your unborn baby. If you use CUTIVATE® Ointment during pregnancy, use CUTIVATE® Ointment on the smallest area of the skin and for the shortest time needed.

are breastfeeding or plan to breastfeed. It is not known if CUTIVATE® Ointment can pass into your breast milk and harm your baby. Breastfeeding women should use CUTIVATE® Ointment on the smallest area of skin and for the shortest time needed. Do not apply CUTIVATE® Ointment directly to the nipple and areola to avoid contact with your baby.

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What are possible side effects with CUTIVATE® Ointment? CUTIVATE® Ointment may cause serious side effects, including:

CUTIVATE® Ointment can pass through your skin and may cause adrenal gland problems. This is more likely to happen if you use CUTIVATE® Ointment for too long, use it over a large treatment area, use it with other topical medicines that contain corticosteroids, cover the treated area, or have liver failure. Your healthcare provider may do blood tests to check your adrenal gland function during and after treatment with CUTIVATE® Ointment.
Skin problems, including skin reactions or thinning of your skin (atrophy), skin infections, and allergic reactions (allergic contact dermatitis) at the treatment site. Tell your healthcare provider if you get any skin reactions such as pain, tenderness, swelling, or healing problems.

Vision Problems. Topical corticosteroids including CUTIVATE® Ointment may increase your chance of developing cataract(s) and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with CUTIVATE® Ointment.

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