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.

AMJEVITA (BLA-761024)

(ADALIMUMAB-ATTO)

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

Download Data

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10/16/2025 (SUPPL-26)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

. . .

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 (14.11, 14.12)]. 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.

. . .

7 Drug Interactions

7.1 Methotrexate

Additions and/or revisions underlined:

Adalimumab has been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent clearance of adalimumab, the data do not suggest the need for dose adjustment of either AMJEVITA or MTX [see Clinical Pharmacology (12.3)].

7.4 Cytochrome P450 Substrates

Additions and/or revisions underlined:

The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha, IL-6) during chronic inflammation. It is possible for products that antagonize cytokine activity, such as adalimumab products, to influence the formation of CYP450 enzymes. Upon initiation or discontinuation of AMJEVITA in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

8 Use in Specific Populations

8.4 Pediatric Use

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

The safety and effectiveness of AMJEVITA 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 AMJEVITA demonstrates that AMJEVITA is safe and effective for pediatric patients in an indication for which HUMIRA (adalimumab) is approved. However, AMJEVITA is not approved for such indication due to marketing exclusivity for HUMIRA (adalimumab).

. . .

Juvenile Idiopathic Arthritis

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

Pediatric Crohn’s Disease

The safety and effectiveness of AMJEVITA 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 AMJEVITA for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data 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 AMJEVITA have not been established in pediatric patients with Crohn’s disease less than 6 years of age.

Pediatric Uveitis

The safety and effectiveness of AMJEVITA for the treatment of non-infectious, intermediate, posterior, and panuveitis have been established in pediatric patients 2 years of age and older. Use of AMJEVITA 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 (14.12)]. The safety and effectiveness of AMJEVITA have not been established in pediatric patients with uveitis less than 2 years of age.

Hidradenitis Suppurativa

Use of AMJEVITA 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 (2.6), Clinical Pharmacology (12.3), and Clinical Studies (14.10)].

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

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

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

What is AMJEVITA?

AMJEVITA is a medicine called a Tumor Necrosis Factor (TNF) blocker. AMJEVITA 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.

. . .

09/17/2025 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Serious Infections

Additions and/or revisions underlined:

. . .

Prior to initiating AMJEVITA, assess if treatment for latent tuberculosis is needed; and consider an induration of greater than or equal to 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).

. . .

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 AMJEVITA, discontinue treatment and evaluate the patient.

6 Adverse Reactions

6.2 Immunogenicity

Additions and/or revisions underlined:

. . .

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

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

. . .

Juvenile Idiopathic Arthritis

The safety and effectiveness of adalimumab products 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) in patients 4 to 17 years of age [see Clinical Studies (14.2)] and a safety study (Study

JIA-II), in patients 2 to less than 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)].

. . .

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)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

For patients who will use the AMJEVITA SureClick autoinjector, tell them that they:

May hear or feel a ‘click’ when the light blue-colored start button is pressed.
Must keep holding the AMJEVITA SureClick autoinjector against their pinched, raised skin until all of the medicine is injected. This can take up to 10 seconds for the
40 mg/0.4 mL and 40 mg/0.8 mL, and up to 15 seconds for the 80 mg/0.8 mL.

Will know that the injection has finished when the window is fully yellow.

. . .

08/20/2024 (SUPPL-19)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

Additions and revisions underlined:

07/12/2023 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and/or revisions underlined:

…

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 AMJEVITA.

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. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1 Rates of lymphoma in clinical trials of adalimumab cannot be compared to rates of lymphoma in clinical trials of other TNF-blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.

…

5.5 Neurologic Reactions

Additions and/or 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 AMJEVITA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of AMJEVITA 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

Changes to table 2; please refer to label

Additions and/or revisions underlined:

…

Infections

In the controlled portions of 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 a subgroup of 10,113 U.S. and Canadian adalimumab-treated patients, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years.

…

Liver Enzyme Elevations

…

In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult patients with CD with a control period duration ranging from 4 to 52 weeks, ALT elevations ? 3 × ULN occurred in 0.9% of adalimumab-treated patients and 0.9% of control-treated patients. In the Phase 3 trial of adalimumab in pediatric patients with Crohn’s disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations ? 3 × ULN occurred in 2.6% (5/192) of patients, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these patients discontinued due to abnormalities in ALT tests. In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ? 3 × ULN occurred in 1.5% of adalimumab-treated patients and 1.0% of control-treated patients. In controlled Phase 3 trials of adalimumab (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ? 3 × ULN occurred in 1.8% of adalimumab-treated patients and 1.8% of control-treated patients. In controlled trials of adalimumab (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations ? 3 x ULN occurred in 0.3% of adalimumab-treated subjects and 0.6% of control-treated subjects. 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 Clinical Studies (14.10)]. The safety profile for patients with UV treated with adalimumab was similar to the safety profile seen in patients with RA.

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is AMJEVITA?

…

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

…

03/22/2023 (SUPPL-12)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and/or revisions underlined:

…

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 another indication, 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 another indication, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma.

…

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 another indication, 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.

…

Lymphoma and Leukemia

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and or revisions underlined:

Infections

In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and another indication, 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.

…Tuberculosis and Opportunistic Infections

In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS, and another indication 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 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations greater than or equal to 3 x ULN occurred in 0.3% of adalimumab-treated subjects and 0.6% of control- treated subjects.

…

Hidradenitis Suppurativa Clinical Studies

Adalimumab has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebo-controlled studies and one open-label extension study [see Clinical Studies (14.9)]. The safety profile for subjects with HS treated with adalimumab weekly was consistent with the known safety profile of adalimumab.

Flare of HS, defined as greater than or equal to 25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from adalimumab treatment following the primary efficacy timepoint in two studies.

6.2 Immunogenicity

Addition of Hidradenitis Suppurativa to the indications section of Table 2; please refer to label for complete information

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 AMJEVITA 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 AMJEVITA and other biologic products for the treatment of RA, PsA, AS, CD, UC, Ps, and HS.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

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

MEDICATION GUIDE

Additions and/or revisions underlined

…

What is AMJEVITA?

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

To reduce the signs and symptoms of:
…

moderate to severe hidradenitis suppurativa (HS) in adults
…
What should I tell my doctor before taking AMJEVITA?
AMJEVITA may not be right for you. Before starting AMJEVITA, tell your doctor about all of your medical conditions, including if you:

are allergic to rubber or latex. The needle cover on the prefilled SureClick® autoinjector contains dry natural rubber. Tell your doctor if you have any allergies to rubber or latex.
…

07/28/2022 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and/or revisions underlined

…

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) and other indications, 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 and other indications, 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

…

Non-Melanoma Skin Cancer

During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps and other indications, 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 AMJEVITA.

Lymphoma and Leukemia

…

5.7 Increased Risk of Infection When Used with Anakinra

Subsection title revised (additions underlined)

Concurrent use of anakinra (an interleukin-1 antagonist) and another TNF-blocker, was associated with a greater proportion of serious infections and neutropenia and no added benefit compared with the TNF-blocker alone in patients with RA. Therefore, the combination of AMJEVITA and anakinra is not recommended

5.11 Increased Risk of Infection When Used with Abatacept

Subsection title revised (additions underlined)

In controlled trials, the concurrent administration of TNF-blockers and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA.

Therefore, the combination of abatacept with TNF-blockers including AMJEVITA is not recommended

[see Drug Interactions (7.2)].

6 Adverse Reactions

Addition of the following to the bulleted line listing:

• Hypersensitivity Reactions [see Warnings and Precautions (5.3)]

• Hepatitis B Virus Reactivation [see Warnings and Precautions (5.4)]

• Neurologic Reactions [see Warnings and Precautions (5.5)]

• Hematological Reactions [see Warnings and Precautions (5.6)]

• Heart Failure [see Warnings and Precautions (5.8)]

• Autoimmunity [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Extensive additions and/or revisions, please refer to label for complete information.

6.2 Immunogenicity

New subsection created

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other adalimumab products may be misleading. There are two assays that have been used to measure anti-adalimumab antibodies. With the ELISA, antibodies to adalimumab could be detected only when serum adalimumab concentrations were < 2 mcg/mL. The ECL assay can detect anti-adalimumab antibody titers independent of adalimumab concentrations in the serum samples. The incidence of anti-adalimumab antibody (AAA) development in patients treated with adalimumab are presented in Table 2.

Please refer to label to view Table 2.

Rheumatoid Arthritis and Psoriatic Arthritis: Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab using the ELISA during the 6- to 12-month period. No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among

antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of adalimumab products is unknown.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined

The safety and effectiveness of AMJEVITA 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.
…
Juvenile Idiopathic Arthritis
In Study JIA-I, adalimumab was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age [see Clinical Studies (14.2)]. In Study JIA-II, the safety profile for patients 2 to < 4 years of age was similar to the safety profile for patients 4 to 17 years of age with polyarticular JIA [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 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 adalimumab products have not been established in pediatric patients with JIA less than 2 years of age.
Pediatric Crohn’s Disease
The safety and effectiveness of adalimumab products 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 adalimumab products for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data 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 adalimumab products have not been established in pediatric patients with Crohn’s disease less than 6 years of age.

8.5 Geriatric Use

Additions and/or revisions underlined

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Consider the benefits and risks of AMJEVITA in patients 65 years of age and older. In patients treated with AMJEVITA, closely monitor for the development of infection or malignancy [see Warnings and Precautions (5.1, 5.2)].

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

MEDICATION GUIDE

Additions and/or revisions underlined

What is AMJEVITA?

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

To reduce the signs and symptoms of:
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moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years and older. AMJEVITA can be used alone or with methotrexate.
psoriatic arthritis (PsA) in adults. AMJEVITA can be used alone or with certain other medicines.
ankylosing spondylitis (AS) in adults.

To treat moderate to severe Crohn’s disease (CD) in adults and children 6 years of age and older .
To treat moderate to severe ulcerative colitis (UC) in adults. It is not known if adalimumab products are effective in people who stopped responding to or could not tolerate TNF-blocker medicines.
…
What should I tell my doctor before takingAMJEVITA?
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are allergic to AMJEVITA or to any of its ingredients. The AMJEVITA prefilled syringe and prefilled SureClick autoinjector are not made with natural rubber latex. See the end of this Medication Guide for a list of ingredients in AMJEVITA.

…

06/13/2019 (SUPPL-4)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: SERIOUS INFECTIONS and MALIGNANCY SERIOUS INFECTIONS

Patients treated with adalimumab products including AMJEVITA …

5 Warnings and Precautions

5.1 Serious Infections

Additions and/or revisions underlined:

Patients treated with adalimumab products including AMJEVITA …

Tuberculosis

‘Adaluminab products’ replaces AMJEVITA.

6 Adverse Reactions

6.2 Postmarketing Experience

Addition of ‘lichenoid skin reaction’ to the Skin Reactions section.

8 Use in Specific Populations

8.1 Pregnancy

8.2 Lactation

PLLR conversion, please refer to label for complete information.

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

MEDICATION GUIDE

Newly added; please refer to label for complete information.