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.

YUFLYMA (BLA-761219)

(ADALIMUMAB-AATY)

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

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10/16/2025 (SUPPL-18)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Autoimmunity

Additions and/or revisions underlined:

Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome or autoimmune hepatitis [see Adverse Reactions (6.1, 6.3)]. If a patient develops symptoms and findings suggestive of a lupus-like syndrome or autoimmune hepatitis following treatment with YUFLYMA, discontinue treatment and evaluate the patient.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

. . .

Less Common Adverse Reactions in Rheumatoid Arthritis Clinical Studies

Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in adalimumab-treated subjects in RA studies (RA-I, RA-II, RA-III, and RA-IV) were:

Body As A Whole: Pain in extremity, pelvic pain, surgery, thorax pain

Cardiovascular System: Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia

. . .

Uveitis Clinical Studies

Adalimumab has been studied in 464 adult subjects with uveitis (UV) in placebo-controlled and open- label extension studies and in 90 pediatric subjects with uveitis (Study PUV-I) [see Clinical Studies (14.10, 14.11)]. The safety profile for subjects with UV treated with adalimumab was similar to the safety profile seen in subjects with RA.

6.2 Immunogenicity

Additions and/or revisions underlined:

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of adalimumab or of other adalimumab products.

. . .

6.3 Postmarketing Experience

Additions and/or revisions underlined:

. . .

Hepato-biliary disorders: Liver failure, hepatitis, autoimmune hepatitis

. . .

7 Drug Interactions

7.2 Biological Products

Additions and/or revisions underlined:

In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of YUFLYMA with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions (5.7, 5.11)]. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of YUFLYMA and other biologic products for the treatment of RA, PsA, AS, CD, UC, Ps, HS and UV. Concomitant administration of YUFLYMA with other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of YUFLYMA have not been established in pediatric patients with psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis.

The safety and effectiveness of YUFLYMA have been established for:

reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older.
the treatment of moderately to severely active Crohn’s disease in pediatric patients 6 years of age and older.
the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
the treatment of non-infectious intermediate, posterior, and panuveitis in pediatric patients 2 years of age and older.

A pediatric assessment for YUFLYMA demonstrates that YUFLYMA is safe and effective for pediatric patients in an indication for which Humira (adalimumab) is approved. However, YUFLYMA is not approved for such indication due to marketing exclusivity for Humira (adalimumab).

. . .

Juvenile Idiopathic Arthritis

The safety and effectiveness of YUFLYMA for the treatment of moderately to severely active polyarticular JIA have been established in pediatric patients 2 years of age and older. Use for this indication is supported by evidence from an adequate and well-controlled study (Study JIA) of adalimumab in patients 4 to 17 years of age [see Clinical Studies (14.2)] and a safety study (Study JIA- II) of adalimumab in patients 2 to <4 years of age where the safety profile was similar to patients 4 to 17 years of age [see Adverse Reactions (6.1)]. Adalimumab products have not been studied in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg.

The safety of adalimumab in pediatric patients in the polyarticular JIA trials was generally similar to that observed in adults with certain exceptions [see Adverse Reactions (6.1)].

The safety and effectiveness of YUFLYMA have not been established in pediatric patients with JIA less than 2 years of age.

. . .

Pediatric Uveitis

The safety and effectiveness of YUFLYMA for the treatment of non-infectious, intermediate, posterior, and panuveitis have been established in pediatric patients 2 years of age and older. Use of YUFLYMA for this indication is supported by evidence from adequate and well-controlled studies of adalimumab in adults and a 2:1 randomized, controlled clinical study of adalimumab in 90 pediatric patients [see Clinical Studies (14.11)]. The safety and effectiveness of YUFLYMA have not been established in pediatric patients with uveitis less than 2 years of age.

Hidradenitis Suppurativa

Use of YUFLYMA in pediatric patients 12 years of age and older for the treatment of moderate to severe HS is supported by evidence from adequate and well-controlled studies of adalimumab in adult HS patients. Additional population pharmacokinetic modeling and simulation predicted that weight- based dosing of adalimumab in pediatric patients 12 years of age and older can provide generally similar exposure to adult HS patients. The course of HS is sufficiently similar in adult and adolescent patients to allow extrapolation of data from adult to adolescent patients. The recommended dosage in pediatric patients 12 years of age or older is based on body weight [see Dosage and Administration (2.7), Clinical Pharmacology (12.3), and Clinical Studies (14.9)].

The safety and effectiveness of YUFLYMA have not been established in patients less than 12 years of age with HS.

8.5 Geriatric Use

Additions and/or revisions underlined:

In clinical studies of RA (Studies RA-I, RA-II, RA-III, and RA-IV), a total of 519 subjects 65 years of age and older, including 107 subjects 75 years of age and older, received adalimumab. No overall difference in effectiveness was observed between these subjects and younger adult subjects.

. . .

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

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

What is YUFLYMA?

YUFLYMA is a medicine called a Tumor Necrosis Factor (TNF) blocker. YUFLYMA is used:

To reduce the signs and symptoms of:

. . .

moderate to severe hidradenitis suppurativa (HS) in people 12 years and older.

. . .

To treat non-infectious intermediate, posterior, and panuveitis in adults and children 2 years of age and older.

. . .

08/16/2024 (SUPPL-11)

Approved Drug Label (PDF)

Other

YUFLYMA changed to Adalimumab-aaty all throughout the label.

12/22/2023 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Malignancies

Additions and revisions underlined:

Consider the risks and benefits of TNF-blocker treatment including YUFLYMA prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF blocker in patients who develop a malignancy.

Malignancies in Adults

In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult patients compared to control-treated adult patients. During the controlled portions of 39 global adalimumab clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS) and uveitis (UV), malignancies, other than non- melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% confidence interval) of 0.7 (0.48, 1.03) per 100 patient-years among 7973 adalimumab-treated patients versus a rate of 0.7 (0.41, 1.17) per 100 patient-years among 4848 control-treated patients (median duration of treatment of 4 months for adalimumab-treated patients and 4 months for control-treated patients). In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in adalimumab-treated patients in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1

In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., patients with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.

Non-Melanoma Skin Cancer

During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with YUFLYMA.

Lymphoma and Leukemia

In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated patients compared to control-treated patients. In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, 2 lymphomas occurred among 7973 adalimumab- treated patients versus 1 among 4848 control-treated patients. In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV with a median duration of approximately 0.7 years, including 24,605 patients and over 40,215 patient-years of adalimumab, the observed rate of lymphomas was approximately 0.11 per 100 patient-years.

5.5 Neurologic Reactions

Additions and revisions underlined:

Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of YUFLYMA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of YUFLYMA should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and revisions underlined:

. . .

Infections

In the controlled portions of the 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 adalimumab-treated patients versus a rate of 2.9 per 100 patient-years in 4848 control- treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions (5.1)].

Tuberculosis and Opportunistic Infections

In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS and UV that included 24,605 adalimumab-treated patients, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient- years.

In controlled trials of adalimumab (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in adult patients with uveitis with an exposure of 165.4 PYs and 119.8 PYs in adalimumab-treated and control-treated patients, respectively, ALT elevations ? 3 x ULN occurred in 2.4% of adalimumab-treated patients and 2.4% of control-treated patients.

. . .

Uveitis Clinical Studies

Adalimumab has been studied in 464 adult patients with uveitis (UV) in placebo-controlled and open-label extension studies [see 14.10)]. The safety profile for patients with UV treated with adalimumab was similar to the safety profile seen in patients with RA.

6.2 Immunogenicity

Addition of Non-infectious Uveitis to table 2

8 Use in Specific Populations

8.4 Pediatric Use

Additions and revisions underlined:

The safety and effectiveness of YUFLYMA have been established for:

reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older.
the treatment of moderately to severely active Crohn’s disease in pediatric patients 6 years of age and older.

Pediatric assessments for Yuflyma demonstrate that Yuflyma is safe and effective for pediatric patients in indications for which Humira (adalimumab) is approved. However, Yuflyma is not approved for such indications due to marketing exclusivity for Humira (adalimumab).

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

Medication Guide

Additions and revisions underlined:

What is YUFLYMA?

. . .

-To treat non-infectious intermediate, posterior, and panuveitis in adults.

11/30/2023 (SUPPL-2)

Approved Drug Label (PDF)

Other

Drug product name revised from “Yuflyma” to “Adalimumab-aaty” all throughout the label.

10/02/2023 (SUPPL-1)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

…

Juvenile Idiopathic Arthritis

…

The safety and effectiveness of YUFLYMA have not been established in pediatric patients with JIA less than 2 years of age.

Pediatric Crohn’s Disease

The safety and effectiveness of YUFLYMA for the treatment of moderately to severely active Crohn’s disease have been established in pediatric patients 6 years of age and older. Use of YUFLYMA for this indication is supported by YUFLYMA’s approval as a biosimilar to adalimumab and evidence from adequate and well-controlled studies in adults with additional data of adalimumab from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [see Adverse Reactions (6.1), Clinical Pharmacology (12.2, 12.3), Clinical Studies (14.6)]. The adverse reaction profile in patients 6 years to 17 years of age was similar to adults.

The safety and effectiveness of YUFLYMA have not been established in pediatric patients with Crohn’s disease less than 6 years of age.

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

MEDICATION GUIDE

Additions and/or revisions underlined:

How should I store YUFLYMA?

…

If needed, for example when you are traveling, you may also store YUFLYMA at room

temperature up to 77°F (25°C) for up to 31 days. Store YUFLYMA in the original carton until use to protect it from light.

…

What are the ingredients in YUFLYMA? Active ingredient: adalimumab-aaty

YUFLYMA AI 40 mg/0.4 mL, YUFLYMA 40 mg/0.4 mL prefilled syringe with safety guard, and YUFLYMA 40 mg/0.4 mL prefilled syringe, YUFLYMA AI 80 mg/0.8 mL, YUFLYMA 80 mg/0.8 mL prefilled syringe with safety guard, YUFLYMA 80 mg/0.8 mL prefilled syringe, and YUFLYMA 20 mg/0.2 mL prefilled syringe: