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receiving a TNF-antagonist including Humira, who are chronic carriers of this virus (i.e., surface antigen positive)when receiving a TNF-antagonist including Humira. Some cases have had a fatal outcome. Patients at risk for HBV infection should be evaluatedtested for prior evidence of HBV infection before initiating treatment with Humira. therapy. For patients who test positive for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.

treatingthe treatment of patients who are carriers of HBV with antiviral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, Humira should be stopped and effective antiviral therapy with appropriate supportive treatment should be initiated.

Malignancies and lymphoproliferative disorders
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on concomitant treatment with azathioprine or 6-mercaptopurine used for Crohn’s disease. The potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira cannot be excluded (see section 4.8).

Section 4.6 Pregnancy and lactation
Pregnancy

For Humira, nolimited clinical data on exposed pregnancies are available In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity and fertility effects of adalimumab are not available (see section 5.3).

Due to its inhibition of TNF

α, adalimumab administered during pregnancy could affect normal immune responses in the newborn. Administration of adalimumab is not recommended during pregnancy. Women of childbearing potential are strongly recommended to use adequate contraception to prevent pregnancy and continue its use for at least five months after the last Humira treatment.

Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of live vaccines to infants exposed to adalimumab in utero is not recommended for at least 5 months following the mother’s last adalimumab injection during pregnancy.

Lactation

It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion. However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last Humira treatment.

Section 10: date of revison

The date of revision has been updated to January 2012

Section 1: addition of : Humira▼ 40 mg/0.8 ml solution for injection for paediatric use
Section 2: addtion of: Each 0.8 ml single dose vial contains 40 mg of adalimumab.
Section 3: addition of: Clear solution for injection in single use vial.
Section 4.1: The JIA indication has been extended from 13-17 years to 4-17 years
Section 4.2: Under JIA a height and weight dosing chart for the 4-12 year age group has been added.
Section 5.1: Updated with EMEA waiver .
Section:6.4: addition of: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the vial in the outer carton.
Section 6.5: updated with information on the vial pack
Section 10: updated with date of revision of SmPC

Section 4.4, Special warnings and precautions for use has been updated to add the text listed below under the following headings

Other opportunistic infections

Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections.

Malignancies and lymphoproliferative disorders

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age), including adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded.

Deletion of the following information

Psoriasis: New-onset and Worsening

Cases of new onset psoriasis, including pustular psoriasis and palmoplantar psoriasis, and cases of worsening of pre-existing psoriasis have been reported with the use of TNF-blockers, including Humira. Many of these patients were taking concomitant immunosuppressants (e.g., MTX, corticosteroids). Some of these patients required hospitalization. Most patients had improvement of their psoriasis following discontinuation of their TNF-blocker. Some patients have had recurrences of the psoriasis when they were re-challenged with a different TNF-blocker. Discontinuation of Humira should be considered for severe cases and those that do not improve or that worsen despite topical treatments.

Section 4.8 Undesirable effects

Leukemia has been added to Table 2

Section 10 Date of revision of text

Has been updated to March 2010

Section 4.4: Update to section under Infections (more information about patients with TB), Serious Infections (new infections added), other Opportunistic infections (more information on infections and signs and symptoms of infections).

Section 4.8: Update to Table 1 and Table 2, section on Neoplasms benign and section under Infections to add extrapulmonary, blastomycosis, coccidioidomycosis, pneumocystis and candidiasis and delete pneumocystis carinii pneumonia.

Section 5.1:  Typographical changes

Section 6.3: Update to shelf life