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.

OTULFI (BLA-761379)

(USTEKINUMAB-AAUZ)

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

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01/15/2026 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Serious Hypersensitivity Reactions

Subsection title revised

Additions and/or revisions underlined:

Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of Ustekinumab products [see Adverse Reactions (6.1, 6.3)]. If a severe or clinically significant hypersensitivity reaction occurs, discontinue OTULFI immediately and initiate appropriate medical treatment [see Contraindications (4)].

6 Adverse Reactions

Additions and/or revisions underlined:

The following serious adverse reactions are discussed elsewhere in the label:

Infections [see Warnings and Precautions (5.1)]
Malignancies [see Warnings and Precautions (5.4)]
Serious Hypersensitivity Reactions [see Warnings and Precautions (5.5)]
Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.6)]
Noninfectious Pneumonia [see Warnings and Precautions (5.8)]

6.3 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been reported during post-approval use of ustekinumab products. 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 ustekinumab product exposure.

Immune system disorders: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, dyspnea, rash, urticaria), including a fatal case that presented with chest tightness and dyspnea during infusion of the first dose.

…

7 Drug Interactions

7.1 Concomitant Therapies

Additions and/or revisions underlined:

In trials in subjects with plaque psoriasis, the safety of ustekinumab products in combination with immunosuppressive agents or phototherapy has not been evaluated. In trials in subjects with psoriatic arthritis, concomitant MTX use did not appear to influence the safety or efficacy of ustekinumab. In trials in subjects with Crohn’s disease (CD-1 and CD-2) and ulcerative colitis (UC-1), immunomodulators (6-MP, AZA, MTX) were used concomitantly in approximately 30% of subjects and corticosteroids were used concomitantly in approximately 40% and 50% of Crohn’s disease and ulcerative colitis subjects, respectively. Use of these concomitant therapies did not appear to influence the overall safety or efficacy of ustekinumab.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Available data from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry, published literature and pharmacovigilance in pregnant women have not identified a ustekinumab associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes (see Data). There are risks to the mother and the fetus associated with inflammatory bowel disease (IBD) in pregnancy. In animal reproductive and developmental toxicity studies, no adverse developmental effects were observed in offspring after administration of ustekinumab to pregnant monkeys at exposures greater than 100 times the maximum recommended human dose (MRHD).

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 of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-associated Maternal and Embryo/Fetal Risk

Published data suggest that the risk of adverse pregnancy outcomes in women with IBD is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Fetal/Neonatal Adverse Reactions

Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, ustekinumab products may be present in infants exposed in utero. The potential clinical impact of ustekinumab product exposure in infants exposed in utero should be considered.

Data

Human Data

An observational pregnancy registry conducted by (OTIS)/MotherToBaby in the U.S. and Canada (enrollment between 2013 and 2019) assessed the risk of major birth defects, pattern of major and minor anomalies in live-born infants, miscarriage, and adverse infant outcomes in women with ustekinumab exposure. In the registry study, there were 101 participants and 107 pregnancies with exposure to ustekinumab (88 prospective; 19 retrospective). Most participants had a primary indication of CD (65.4%) or psoriasis (30.8%). The pregnancy registry did not identify a ustekinumab associated risk of major birth defects, pattern of major or minor anomalies, increased risk of miscarriage or adverse infant outcomes. Methodological limitations of the registry include small sample size, lack of an internal comparison group, a mix of prospective and retrospective reports, and unmeasured confounders. The conclusions from the pregnancy registry were consistent with the published literature and pharmacovigilance.

…

8.4 Pediatric Use

Additions and/or revisions underlined:

Plaque Psoriasis

The safety and effectiveness of OTULFI have been established for the treatment of moderate to severe plaque psoriasis in pediatric patients 6 years of age and older who are candidates for phototherapy or systemic therapy.

Use of OTULFI in pediatric patients 12 to less than 17 years of age is supported by evidence from a multicenter, randomized, 60-week trial (Ps STUDY 3) of ustekinumab that included a 12-week, double-blind, placebo-controlled, parallel-group portion, in 110 pediatric subjects 12 years of age and older [see Adverse Reactions (6.1), Clinical Studies (14.2)].

Use of OTULFI in pediatric patients 6 to 11 years of age is supported by evidence from an open-label, single-arm, efficacy, safety and pharmacokinetics trial (Ps STUDY 4) of ustekinumab in 44 subjects [see Adverse Reactions (6.1), Pharmacokinetics (12.3)].

The safety and effectiveness of OTULFI have not been established in pediatric patients less than 6 years of age with plaque psoriasis.

Psoriatic Arthritis

The safety and effectiveness of OTULFI have been established for treatment of psoriatic arthritis in pediatric patients 6 years of age and older.

Use of OTULFI in these age groups is supported by evidence from adequate and well controlled trials of ustekinumab in adult subjects with psoriasis and PsA, pharmacokinetic data from adult subjects with psoriasis, adult subjects with PsA and pediatric subjects with psoriasis, and safety data of ustekinumab from two clinical trials in 44 pediatric subjects 6 to 11 years old with psoriasis and 110 pediatric subjects 12 years of age and older with psoriasis. The observed pre-dose (trough) concentrations are generally comparable between adult subjects with psoriasis, adult subjects with PsA and pediatric subjects with psoriasis, and the PK exposure is expected to be comparable between adult and pediatric subjects with PsA [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2, 14.3)].

The safety and effectiveness of OTULFI have not been established in pediatric patients less than 6 years old with psoriatic arthritis.

Crohn’s Disease and Ulcerative Colitis

The safety and effectiveness of OTULFI have not been established in pediatric patients with Crohn’s disease or ulcerative colitis.

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

MEDICATION GUIDE

Extensive changes; please refer to label for complete information

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Serious Hypersensitivity and Reactions

Inform patients that serious hypersensitivity reactions have been reported with intravenous and subcutaneous administration of ustekinumab products. Instruct patients to discontinue OTULFI and seek immediate medical attention if they experience any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.5)].

…

02/19/2025 (SUPPL-3)

Approved Drug Label (PDF)

7 Drug Interactions

7.2 CYP450 Substrates

Additions and revisions underlined:

The formation of CYP450 enzymes can be suppressed by increased levels of certain cytokines (e.g., IL-1, IL-6, TNF?, IFN) during chronic inflammation. Thus, use of ustekinumab products, antagonists of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of OTULFI in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and adjust the individual dosage of the CYP substrate as needed. See the prescribing information of specific CYP substrates.

A CYP-mediated drug interaction effect was not observed in subjects with Crohn’s disease [see Clinical Pharmacology (12.3)].