Important Safety Information

Globally, prescribing information varies; refer to the individual countryproduct label for complete information.

Serious infections, sepsis, rare cases of tuberculosis (TB), andopportunistic infections, including fatalities, have been reported with theuse of TNF antagonists, including HUMIRA. Many of the serious infections haveoccurred in patients on concomitant immunosuppressive therapy that, inaddition to their underlying disease could predispose them to infections.Patients must be monitored closely for infections, including tuberculosis,before, during and after treatment with HUMIRA. Treatment should not beinitiated in patients with active infections until infections are controlled.HUMIRA should not be used by patients with active TB or other severeinfections such as sepsis and opportunistic infections. Patients who developnew infections while using HUMIRA should be monitored closely. HUMIRA shouldbe discontinued if a patient develops a new serious infection until infectionsare controlled. Physicians should exercise caution when considering use ofHUMIRA in patients with a history of recurring infection or with underlyingconditions that may predispose patients to infections.

TNF-blocking agents have been associated with reactivation of hepatitis B(HBV) in patients who are chronic carriers of the virus. Some cases have beenfatal. Patients at risk for HBV infection should be evaluated for priorevidence of HBV infection before initiating HUMIRA.

The combinations of HUMIRA and anakinra as well as HUMIRA and abatacept isnot recommended.

TNF antagonists, including HUMIRA, have been associated in rare cases withdemyelinating disease and serious allergic reactions. Rare reports ofpancytopenia including aplastic anemia have been reported with TNF-blockingagents. Adverse events of the haematologic system, including medicallysignificant cytopenia have been infrequently reported with HUMIRA.

More cases of malignancies including lymphoma have been observed amongpatients receiving a TNF antagonist compared with control patients in clinicaltrials. The size of the control group and limited duration of the controlledportions of studies precludes the ability to draw firm conclusions.Furthermore, there is an increased background lymphoma risk in rheumatoidarthritis patients with long-standing, highly active, inflammatory disease,which complicates the risk estimation. During the long-term open-label trialswith HUMIRA, the overall rate of malignancies was similar to what would beexpected for an age, gender and race matched general population. With thecurrent knowledge, a possible risk for the development of lymphomas or othermalignancies in patients treated with a TNF antagonist cannot be excluded.All patients, and in particular patients with a medical history of extensiveimmunosuppressant therapy or psoriasis patients with a history of PsoralenUltra-Violet A (PUVA) treatment, should be examined for the presence ofnon-melanoma skin cancer prior to and during treatment with HUMIRA.

In clinical studies with another TNF antagonist, a higher rate of seriouscongestive heart failure (CHF) related adverse events including worsening CHFand new onset CHF have been reported. Cases of worsening CHF have also beenreported in patients receiving HUMIRA. Physicians should exercise cautionwhen using HUMIRA in patients who have heart failure and monitor themcarefully. HUMIRA should not be used in patients with moderate or severeheart failure.

The most frequently reported adverse event (>1/10 patients) at leastpossibly causally related to HUMIRA is injection site reaction (includingpain, swelling, redness or pruritus).