Serious Infections and Malignancy
Patients treated with Adalimumab are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue Adalimumab if a patient develops a serious infection or sepsis.
Reported infections include:
- Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before Adalimumab use and during therapy. Initiate treatment for latent TB prior to Adalimumab use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.
Carefully consider the risks and benefits of treatment with Adalimumab prior to initiating therapy in patients with chronic or recurrent infection.
Monitor patients closely for the development of signs and symptoms of infection during and after treatment with Adalimumab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy (see Warnings and Precautions and Adverse Reactions).
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including Adalimumab (see Warnings and Precautions).
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including Adalimumab. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants (see Warnings and Precautions).
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Evaluate patients for latent TB with tuberculin skin testing
- Treat latent tuberculosis infection prior to therapy with adalimumab.
- Monitor patients receiving adalimumab for signs and symptoms of active TB, including those who are TB skin test negative.
- Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy, that in addition, to their rheumatoid arthritis, could predisopse them to infections.
- Do not initiate adalimumab in patients with active infections (chronic or localized).
- Patients who develop new infections during therapy should be monitored closely.
- Discontinue adalimumab if patient develops a serious infection.
- Exercise caution when considering the use of this drug in patients with a history of recurrent infection or underlying conditions which may predispose to infections or patients who have resided in regions where TB and histoplasmosis are endemic (See PRECAUTIONS).
- The benefits and risk of adalimumab treatment should be carefully considered before intiation of therapy.
PATIENT CARE PLAN
FDA and Industry Communications
- FDA Information on TNF Blockers
- Boxed Warning Revision for TNF Blockers: Addition of Risk of Listeria and Legionella Bacterial Infection (Sept 2011)
- Safety Review Update on Reports of Hepatosplenic T-Cell Lymphoma in Adolescents and Young Adults Receiving TNF Blockers, Azathioprine and/or Mercaptopurine (April 2011)
- Boxed Warning Revision: TNF Blockers (November 2009)
- Revised Boxed Warnings Planned per FDA Safety Review: Increased Risk of Lymphomas and Other Malignancies in Children/Adolescents Treated with TNF Blockers (August 2009)
Patient Counseling Information