WARNINGS
SERIOUS INFECTIONS AND SEPSIS, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH THE USE OF TNF BLOCKING AGENTS INCLUDING HUMIRA. MANY OF THE SERIOUS INFECTIONS HAVE OCCURRED IN PATIENTS ON CONCOMITANT IMMUNOSUPPRESSIVE THERAPY THAT, IN ADDITION TO THEIR RHEUMATOID ARTHRITIS, COULD PREDISPOSE THEM TO INFECTIONS. TUBERCULOSIS AND INVASIVE OPPORTUNISTIC FUNGAL INFECTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH TNF BLOCKING AGENTS INCLUDING HUMIRA. TREATMENT WITH HUMIRA SHOULD NOT BE INITIATED IN PATIENTS WITH ACTIVE INFECTIONS INCLUDING CHRONIC OR LOCALIZED INFECTIONS. PATIENTS WHO DEVELOP A NEW INFECTION WHILE UNDERGOING TREATMENT WITH HUMIRA SHOULD BE MONITORED CLOSELY. ADMINISTRATION OF HUMIRA SHOULD BE DISCONTINUED IF A PATIENT DEVELOPS A SERIOUS INFECTION. PHYSICIANS SHOULD EXERCISE CAUTION WHEN CONSIDERING THE USE OF HUMIRA IN PATIENTS WITH A HISTORY OF RECURRENT INFECTION OR UNDERLYING CONDITIONS WHICH MAY PREDISPOSE THEM TO INFECTIONS, OR PATIENTS WHO HAVE RESIDED IN REGIONS WHERE TUBERCULOSIS AND HISTOPLASMOSIS ARE ENDEMIC (see PRECAUTIONS - Tuberculosis and ADVERSE REACTIONS - Infections). THE BENEFITS AND RISKS OF HUMIRA TREATMENT SHOULD BE CAREFULLY CONSIDERED BEFORE INITIATION OF HUMIRA THERAPY.
NEUROLOGIC EVENTS
Use of TNF blocking agents, including HUMIRA, has been associated with rare cases of exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Prescribers should exercise caution in considering the use of HUMIRA in patients with preexisting or recent-onset central nervous system demyelinating disorders.
MALIGNANCIES
Lymphomas have been observed in patients treated with TNF blocking agents including HUMIRA. In clinical trials, patients treated with HUMIRA had a higher incidence of lymphoma than the expected rate in the general population (see ADVERSE REACTIONS - Malignancies). While patients with rheumatoid arthritis, particularly those with highly active disease, may be at a higher risk (up to several fold) for the development of lymphoma, the role of TNF blockers in the development of malignancy is not known. 4,5
PRECAUTIONS
GENERAL
Allergic reactions have been observed in approximately 1% of patients receiving HUMIRA. If an anaphylactic reaction or other serious allergic reaction occurs, administration of HUMIRA should be discontinued immediately and appropriate therapy initiated.
INFORMATION TO PATIENTS
The first injection should be performed under the supervision of a qualified health care professional. If a patient or caregiver is to administer HUMIRA, he/she should be instructed in injection techniques and their ability to inject subcutaneously should be assessed to ensure the proper administration of HUMIRA (see HUMIRA, PATIENT INFORMATION LEAFLET). A puncture-resistant container for disposal of needles and syringes should be used. Patients or caregivers should be instructed in the technique as well as proper syringe and needle disposal, and be cautioned against reuse of these items.
TUBERCULOSIS
As observed with other TNF blocking agents, tuberculosis associated with the administration of HUMIRA in clinical trials has been reported (see WARNINGS). While cases were observed at all doses, the incidence of tuberculosis reactivations was particularly increased at doses of HUMIRA that were higher than the recommended dose. All patients recovered after standard antimicrobial therapy. No deaths due to tuberculosis occurred during the clinical trials.
Before initiation of therapy with HUMIRA, patients should be evaluated for active or latent tuberculosis infection with a tuberculin skin test. If latent infection is diagnosed, appropriate prophylaxis in accordance with the Centers for Disease Control and Prevention guidelines6 should be instituted. Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent cough, wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur.
IMMUNOSUPPRESSION
The possibility exists for TNF blocking agents, including HUMIRA, to affect host defenses against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses. In a study of 64 patients with rheumatoid arthritis treated with HUMIRA, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T- and B-cells and NK-cells, monocyte/macrophages, and neutrophils. The impact of treatment with HUMIRA on the development and course of malignancies, as well as active and/or chronic infections is not fully understood (see WARNINGS, ADVERSE REACTIONS, Infections and Malignancies). The safety and efficacy of HUMIRA in patients with immunosuppression have not been evaluated.
IMMUNIZATIONS
No data are available on the effects of vaccination in patients receiving HUMIRA. Live vaccines should not be given concurrently with HUMIRA. No data are available on the secondary transmission of infection by live vaccines in patients receiving HUMIRA.
AUTOIMMUNITY
Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with HUMIRA, treatment should be discontinued (see ADVERSE REACTIONS, Autoantibodies).
DRUG INTERACTIONS
HUMIRA has been studied in rheumatoid arthritis patients taking concomitant MTX (see CLINICAL PHARMACOLOGY: Drug Interactions). The data do not suggest the need for dose adjustment of either HUMIRA or MTX.
CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
Long-term animal studies of HUMIRA have not been conducted to evaluate the carcinogenic potential or its effect on fertility. No clastogenic or mutagenic effects of HUMIRA were observed in the in vivo mouse micronucleus test or the Salmonella-Escherichia coli (Ames) assay, respectively.
PREGNANCY
Pregnancy Category B--An embryo-fetal perinatal developmental toxicity study has been performed in cynomolgus monkeys at dosages up to 100 mg/kg (266 times human AUC when given 40 mg subcutaneous with MTX every week or 373 times human AUC when given 40 mg subcutaneous without MTX) and has revealed no evidence of harm to the fetuses due to adalimumab. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction and developmental studies are not always predictive of human response, HUMIRA (adalimumab) should be used during pregnancy only if clearly needed.
NURSING MOTHERS
It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from HUMIRA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
PEDIATRIC USE
Safety and effectiveness of HUMIRA in pediatric patients have not been established.
GERIATRIC USE
A total of 519 patients 65 years of age and older, including 107 patients 75 years and older, received HUMIRA in clinical studies. No overall difference in effectiveness was observed between these subjects and younger subjects. The frequency of serious infection and malignancy among HUMIRA treated subjects over age 65 was higher than for those under age 65. Because there is a higher incidence of infections and malignancies in the elderly population in general, caution should be used when treating the elderly.
|
