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Guide
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.
IDACIO (BLA-761255)
(ADALIMUMAB-AACF)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
12/23/2025 (SUPPL-12)
5 Warnings and Precautions
5.9 AutoimmunityAdditions 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 IDACIO, discontinue treatment and evaluate the patient.
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 (14.10, 14.11)]. The safety profile for subjects with UV treated with adalimumab was similar to the safety profile seen in subjects with RA.
6.3 Postmarketing Experience
Additions and/or revisions underlined:
…
Hepato-biliary disorders: Liver failure, hepatitis, autoimmune hepatitis.
…
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of IDACIO have not been established in pediatric patients with psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis.
The safety and effectiveness of IDACIO 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.
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.
…
Juvenile Idiopathic Arthritis
The safety and effectiveness of IDACIO 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.
…
Pediatric Uveitis
The safety and effectiveness of IDACIO for the treatment of non-infectious, intermediate, posterior, and panuveitis have been established in pediatric patients 2 years of age and older. Use of IDACIO 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 IDACIO have not been established in pediatric patients with uveitis less than 2 years of age.
Hidradenitis Suppurativa
Use of IDACIO 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 IDACIO have not been established in patients less than 12 years of age with HSAdditions 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.
…
06/04/2024 (SUPPL-6)
6 Adverse Reactions
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- drugantibodies in other studies, including those of adalimumab or of other adalimumab products.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Instruct patients to dispose of their used needles and syringes or used Pen in a FDA-cleared sharps disposal container immediately after use. Instruct patients not to dispose of loose needles and syringes or Pens in their household trash. Instruct patients that if they do not have a FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.
Instruct patients that when their sharps disposal container is almost full, they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container.
Instruct patients that there may be state or local laws regarding disposal of used needles and syringes.
MEDICATION GUIDE
Additions and/or revisions underlined:
How should I store Adalimumab-aacf?
…
Refrigerated Adalimumab-aacf may be used until the expiration date printed on the Adalimumab-aacf carton. Pen or prefilled syringe. Do not use Adalimumab-aacf after the expiration date.
…
Do not use a Pen or prefilled syringe if the liquid is cloudy, discolored, or has flakes or particles in it.
- Do not drop or crush Adalimumab-aacf. The prefilled syringe is glass.
…
What are the ingredients in Adalimumab-aacf? Active ingredient: adalimumab-aacf
Adalimumab-aacf 40 mg/0.8 mL Pen, Adalimumab-aacf 40 mg/0.8 mL prefilled syringe and Adalimumab-aacf 40 mg/0.8 mL institutional use vial kit.
10/31/2023 (SUPPL-3)
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 versusa 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.
…
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 IDACIO.
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/or revisions underlined:
…
There is a known association between intermediate uveitis and central demyelinating disorders.
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or 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.
…
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 was0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years.
…
Liver Enzyme Elevations
…
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 (Study PUV-I) [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.
6.2 Immunogenicity
Addition of Non-infectious Uveitis to the section Indications of table 2; please refer to label for complete information
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
What is IDACIO?
IDACIO is a medicine called a Tumor Necrosis Factor (TNF) blocker. IDACIO is used:
…
• To treat non-infectious intermediate, posterior, and panuveitis in adults.
10/11/2023 (SUPPL-2)
5 Warnings and Precautions
5.2 MalignanciesAdditions 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. 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, 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. 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 IDACIO.
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 another indication, 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 another indication 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.
…
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or 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 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. 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 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 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. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years.
…
Liver Enzyme Elevations
…
…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.
Other Adverse Reactions
…
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
Immunogenicity data from clinical trials evaluating adalimumab for the treatment of HS was added to Table 2 for alignment with the reference product labeling; please refer to label to view Table 2.
7 Drug Interactions
7.2 Biological ProductsAdditions and/or revisions underlined:
…
there is insufficient information regarding the concomitant use of IDACIO and other biologic products for the treatment of RA, PsA, AS, CD, UC, Ps and HS. Concomitant administration of IDACIO 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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
What is IDACIO?
IDACIO is a medicine called a Tumor Necrosis Factor (TNF) blocker. IDACIO is used:
To reduce the signs and symptoms of:
…
moderate to severe hidradenitis suppurativa (HS) in adults.
…