Drug Safety-related Labeling Changes (SrLC)

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HYRIMOZ (BLA-761071)

(ADALIMUMAB-ADAZ)

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

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10/16/2025 (SUPPL-31)

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.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

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

The safety and effectiveness of HYRIMOZ 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.

. . .

Juvenile Idiopathic Arthritis

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

Hidradenitis Suppurativa

Use of HYRIMOZ 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 (14.10)].

The safety and effectiveness of HYRIMOZ 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 HYRIMOZ?

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

. . .

07/29/2025 (SUPPL-24)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Risk of Death

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 HYRIMOZ, discontinue treatment and evaluate the patient.

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been identified during post-approval use of adalimumab 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 adalimumab products exposure.

. . .

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

. . .

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

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

. . .

Juvenile Idiopathic Arthritis

The safety and effectiveness of HYRIMOZfor 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 < 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)].

. . .

05/20/2025 (SUPPL-22)

Approved Drug Label (PDF)

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

MEDICATION GUIDE

Additions and/or revisions underlined:

How should I store HYRIMOZ?

…

If needed, for example when you are traveling, you may also store the HYRIMOZ 40 mg/0.8 mL single-dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive Needle Guard, the HYRIMOZ 20 mg/0.4 mL single-dose prefilled syringe with BD UltraSafe Passive Needle Guard or the HYRIMOZ 10 mg/0.2 mL single- dose prefilled syringe at room temperature up to 77°F (25°C) for up to 21 days and HYRIMOZ 80 mg/0.8 mL single- dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive Needle Guard, HYRIMOZ 40 mg/0.4 mL single-dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive Needle Guard, HYRIMOZ 20 mg/0.2 mL single-dose prefilled syringe and HYRIMOZ 10 mg/0.1 mL single-dose prefilled syringe for up to 14 days. Store HYRIMOZ in the original carton until use to protect it from light. Throw away HYRIMOZ 40 mg/0.8 mL, HYRIMOZ 20 mg/0.4 mL and HYRIMOZ 10 mg/0.2 mL if it has been kept at room temperature and not been used within 21 days. Throw away HYRIMOZ 80 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.2 mL and 10 mg/0.1 mL if it has been kept at room temperature and not been used within 14 days.

…

What are the ingredients in HYRIMOZ?

Active ingredient: adalimumab-adaz

HYRIMOZ single-dose prefilled Sensoready Pen 40 mg/0.8 mL, HYRIMOZ single-dose prefilled syringe with BD UltraSafe Passive Needle Guard 40 mg/0.8 mL, HYRIMOZ single-dose prefilled syringe with BD UltraSafe Passive Needle Guard 20 mg/0.4 mL and HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe:

Inactive ingredients: adipic acid, citric acid monohydrate, mannitol, polysorbate 80, sodium chloride, and Water for Injection. Hydrochloric acid and sodium hydroxide are added as necessary to adjust pH.

HYRIMOZ single-dose prefilled Sensoready Pen 80 mg/0.8 mL and 40 mg/0.4 mL, HYRIMOZ single-dose prefilled syringe with BD UltraSafe Passive Needle Guard 80 mg/0.8 mL and 40 mg/0.4 mL and HYRIMOZ single-dose prefilled syringe 20 mg/0.2 mL and 10 mg/0.1 mL:

Inactive ingredients: adipic acid, mannitol, polysorbate 80, and Water for Injection. Hydrochloric acid and sodium hydroxide are added as necessary to adjust pH.

04/05/2024 (SUPPL-19)

Approved Drug Label (PDF)

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-drug antibodies in other studies, including those of adalimumab or of other adalimumab products.

…

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

…

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

09/08/2023 (SUPPL-16)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and/or revisions underlined:

…

Malignancies in Adults

…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.

…

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.

…

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).

…

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. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions (5.1)].

…

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 greater than or equal to 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 Study (14.11)] . 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 HYRIMOZ?

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

…

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

…

04/14/2023 (SUPPL-15)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Additions and revisions underlined:

. . .

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 HYRIMOZ.

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 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 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.

. . .

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 (14.10)]. The safety profile for subjects with HS treated with adalimumab weekly was consistent with the known safety profile of adalimumab products.

Flare of HS, defined as ?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

Changes to table to add indication of hidradenitis suppurativa; please refer to label

8 Use in Specific Populations

8.4 Pediatric Use

Newly added information:

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

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

Medication Guide

Additions and revisions underlined:

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

• To reduce the signs and symptoms of:

  • moderate to severe rheumatoid arthritis (RA) in adults. HYRIMOZ can be used alone, with methotrexate, or with certain other medicines.

  • moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years and older. HYRIMOZ can be used alone or with methotrexate.

  • psoriatic arthritis (PsA) in adults. HYRIMOZ can be used alone or with certain other medicines.

  • ankylosing spondylitis (AS) in adults.

  • moderate to severe hidradenitis suppurativa (HS) in adults.

03/20/2023 (SUPPL-14)

Approved Drug Label (PDF)

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

MEDICATION GUIDE

Additions and/or revisions underlined:

How should I store HYRIMOZ?

• If needed, for example when you are traveling, you may also store the HYRIMOZ 40 mg/0.8 mL single-dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive™ Needle Guard, the HYRIMOZ 20 mg/0.4 mL single-dose prefilled syringe with BD UltraSafe Passive™ Needle Guard or the HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe at room temperature up to 77°F (25°C) f or up to 21 days and HYRIMOZ 80 mg/0.8 mL single-dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive™ Needle Guard, HYRIMOZ 40 mg/0.4 mL single-dose prefilled Sensoready Pen or single-dose prefilled syringe with BD UltraSafe Passive™ Needle Guard, HYRIMOZ 20 mg/0.2 mL single-dose prefilled syringe and HYRIMOZ 10 mg/0.1 mL single-dose prefilled syringe for up to 14 days. Store HYRIMOZ in the original carton until use to protect it from light. Throw away HYRIMOZ 40 mg/0.8 mL, HYRIMOZ 20 mg/0.4 mL and HYRIMOZ 10 mg/0.2 mL if it has been kept at room temperature and not been used within 21 days. Throw away HYRIMOZ 80 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.2 mL and 10 mg/0.1 mL if it has been kept at room temperature and not been used within 14 days.

• Record the date you first remove HYRIMOZ from the refrigerator in the spaces provided on the carton.

• Do not store HYRIMOZ in extreme heat or cold.

• The solution should be clear and colorless or slightly yellowish. Do not use HYRIMOZ if the solution is cloudy, discolored, or has flakes or particles in it.

• Do not drop or crush HYRIMOZ. The prefilled syringe is glass.

• The prefilled syringes and injection devices are not made with natural rubber latex.

Keep HYRIMOZ, injection supplies, and all other medicines out of the reach of children.

…

What are the ingredients in HYRIMOZ?

Active ingredient: adalimumab-adaz

HYRIMOZ single-dose pref illed Sensoready Pen 40 mg/0.8 mL, HYRIMOZ single-dose pref illed syringe with BD UltraSafe PassiveTM Needle Guard 40 mg/0.8 mL, HYRIMOZ single-dose pref illed syringe with BD UltraSafe PassiveTM Needle Guard 20 mg/0.4 mL and HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe:

Inactive ingredients: adipic acid, citric acid monohydrate, mannitol, polysorbate 80, sodium chloride, and Water for Injection, USP. Hydrochloric acid and sodium hydroxide are added as necessary to adjust pH.

HYRIMOZ single-dose pref illed Sensoready Pen 80 mg/0.8 mL and 40 mg/0.4 mL, HYRIMOZ single-dose pref illed syringe with BD UltraSafe PassiveTM NeedleGuard 80 mg/0.8 mL and 40 mg/0.4 mL and HYRIMOZ single-dose prefilled syringe 20 mg/0.2 mL and 10 mg/0.1 mL.

Inactive ingredients: adipic acid, mannitol, polysorbate 80, and Water for Injection, USP. Hydrochloric acid and sodium hydroxide are added as necessary to adjust pH.

07/18/2022 (SUPPL-10)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined

… 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 greater than or equal to 3 x 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 greater than or equal to 3 x 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 greater than or equal to  3 x ULN

occurred in 1.8 % of adalimumab-treated patients and 1.8 % of control-treated patients.

…

Crohn’s Disease Clinical Studies

…

Pediatric Patients 6 Years to 17 Years: The safety profile of adalimumab in 192 pediatric patients from one double-blind study (Study PCD-I) and one open-label extension study [see Clinical Studies (14.6)] was similar to the safety profile seen in adult patients with Crohn’s disease.

During the 4-week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with adalimumab were injection site pain and injection site reaction (6% and 5%, respectively).

A total of 67% of children experienced an infection while receiving adalimumab in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis.

A total of 5% of children experienced a serious infection while receiving adalimumab in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis.

In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined

The safety and effectiveness of HYRIMOZ 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 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.

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

MEDICATION GUIDE

Additions and/or revisions underlined

…

What is HYRIMOZ?

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

…

• To treat moderate to severe Crohn’s disease (CD) in adults and children 6 years of age and older.

  …

07/18/2022 (SUPPL-12)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined

…

Liver Enzyme Elevations

… No ALT elevations greater than or equal to 3 x ULN occurred in the open-label study of adalimumab in patients with polyarticular JIA who were 2 to <4 years.

…

Juvenile Idiopathic Arthritis Clinical Studies

…

In Study JIA-II, adalimumab was studied in 32 patients who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with polyarticular JIA. The safety profile for this patient population was similar to the safety profile seen in patients 4 to 17 years of age with polyarticular JIA.

In Study JIA-II, 78% of patients experienced an infection while receiving adalimumab. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of patients receiving adalimumab in the study and included dental caries, rotavirus gastroenteritis, and varicella.

In Study JIA-II, non-serious allergic reactions were observed in 6% of patients and included intermittent urticaria and rash, which were all mild in severity.

…

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined

The safety and effectiveness of HYRIMOZ have been established for:

• Reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 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.

  …

03/28/2022 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignancies

Revisions, please refer to label for complete information

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

  Revisions, please refer to label for complete information

  6.2 Immunogenicity

  New subsection added

  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.

  Table 2: Anti-Adalimumab Antibody Development Determined by ELISA and ECL Assay in Patients Treated with adalimumab

  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 HYRIMOZ have been established for reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 4 years of age and older.

…

8.5 Geriatric Use

Additions underlined

… Consider the benefits and risks of HYRIMOZ in patients 65 years of age and older. In patients treated with HYRIMOZ, 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 underlined

…

• are allergic to rubber or latex. Tell your doctor if you have any allergies to rubber or latex.

  • The following components contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex: the gray needle cap of the HYRIMOZ 40 mg/0.8 mL single-dose prefilled syringe and the gray needle cover within the needle cap of the HYRIMOZ 40 mg/0.8 mL single-dose prefilled Sensoready® Pen.

  • The prefilled syringe of HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe is not made with natural rubber latex

    …

• are pregnant or plan to become pregnant, breastfeeding or plan to breastfeed. You and your doctor should decide if you should take HYRIMOZ while you are pregnant or breastfeeding.

  …

  How should I store HYRIMOZ?

  …

• If needed, for example when you are traveling, you may also store the HYRIMOZ 40 mg/0.8 mL single-dose prefilled Sensoready Pen or the HYRIMOZ 40 mg/0.8 mL single-dose prefilled syringe with BD UltraSafe Passive™ Needle Guard at room temperature up to 77°F (25°C) for up to 14 days. Store HYRIMOZ in the original carton until use to protect it from light. Throw away HYRIMOZ 40 mg/0.8 mL if it has been kept at room temperature and not been used within 14 days.

• If needed, for example when you are traveling, you may also store the HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe at room temperature up to 77°F (25°C) for up to 21 days. Store HYRIMOZ in the original carton until use to protect it from light. Throw away HYRIMOZ 10 mg/0.2 mL if it has been kept at room temperature and not been used within 21 days.

  …

  What are the ingredients in HYRIMOZ? Active ingredient: adalimumab-adaz

  HYRIMOZ single-dose prefilled Sensoready Pen 40 mg/0.8 mL, HYRIMOZ single-dose prefilled syringe with BD UltraSafe PassiveTM Needle Guard 40 mg/0.8 mL and HYRIMOZ 10 mg/0.2 mL single-dose prefilled syringe:

  Inactive ingredients: adipic acid, citric acid monohydrate, mannitol, polysorbate 80, sodium chloride, and Water for Injection, USP. Hydrochloric acid and sodium hydroxide are added as necessary to adjust pH.

   

  …

PATIENT COUNSELING INFORMATION

Additions underlined

…

Hypersensitivity Reactions

Advise patients to seek immediate medical attention if they experience any symptoms of severe hypersensitivity reactions. Advise latex-sensitive patients that the following components contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex: the gray needle cap of the HYRIMOZ 40 mg/0.8 mLsingle-dose prefilled syringe and the gray needle cover within the needle cap of the HYRIMOZ 40 mg/0.8 mL single-dose prefilled Sensoready Pen. HYRIMOZ 10 mg/0.2 mL single- dose prefilled syringe is not made with natural rubber latex [see How Supplied/Storage and Handling (16) for specific information].

…

02/24/2021 (SUPPL-1)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of adalimumab 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 adalimumab products exposure.

Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis

General disorders and administration site conditions: Pyrexia

Hepato-biliary disorders: Liver failure, hepatitis

Immune system disorders: Sarcoidosis

Neoplasms benign, malignant and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)

Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome), cerebrovascular accident

Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism

Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia, lichenoid skin reaction

Vascular disorders: Systemic vasculitis, deep vein thrombosis