Label Changes for:
Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
5 WARNINGS AND PRECAUTIONS
5.1 Serious Infections
- Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving HUMIRA, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate....
- Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with HUMIRA
- The potential risk with the combination of azathioprine or 6-mercaptopurine and HUMIRA should be carefully considered.
5.3 Hypersensitivity Reactions
- Anaphylaxis and angioneurotic edema have been reported following HUMIRA administration. If an anaphylactic or other serious allergic reaction occurs, ......
- It is recommended that JIA patients, if possible, be brought up to date with all immunizations in agreement with current immunization.....
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
- General disorders and administration site conditions: Pyrexia
- Neoplasms benign, malignant and unspecified (incl cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)
7 DRUG INTERACTIONS
7.2 Biologic Products
- Concomitant administration of HUMIRA with other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions.
8 Use In Specific Populations
Pregnancy Category B
- see PI for extensive changes to all subsections
8.3 Nursing Mothers
- Limited data from published literature indicate that adalimumab is present in low levels in human milk and is not likely to be absorbed by a breastfed infant.
8.4 Pediatric Use
- Due to its inhibition of TNFα, HUMIRA administered during pregnancy could affect immune response in the in uteroexposed newborn and infant. Data from five infants exposed....
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
- added...liver failure, sarcoidosis, demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome), cerebrovascular accident, pulmonary embolism, alopecia, and deep vein thrombosis.
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member.
WARNINGS and PRECAUTIONS
- Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which HUMIRA is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.
- In the controlled portions of clinical trials of all the TNF-blocking agents, more cases of lymphoma have been observed among patients receiving TNF blockers compared to control patients. In controlled trials in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and plaque psoriasis, 2 lymphomas were observed among 3853 HUMIRA-treated patients versus 1 among 2183 control patients. In combining the controlled and uncontrolled open-label portions of these clinical trials with a median duration of approximately 2 years, including 6539 patients and over 16,000 patient-years of therapy, the observed rate of lymphomas is approximately 0.11/100 patient-years. This is approximately 3-fold higher than expected in the general population.1 Rates in clinical trials for HUMIRA cannot be compared to rates of clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with rheumatoid arthritis, particularly those with highly active disease, are at a higher risk for the development of lymphoma. Cases of acute and chronic leukemia have been reported in association with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
- Skin reactions: new or worsening psoriasis (all sub-types including pustular and palmoplantar)