Safety profile

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Patients taking TNF-antagonists, including Imraldi™ (adalimumab), are more susceptible to serious infections and impaired lung function may potentiate this risk. Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients receiving adalimumab.

Treatment with Imraldi™ (adalimumab) should not be initiated in patients with active infections, including chronic or localised infections, until these are controlled. Patients developing a new infection while undergoing treatment with Imraldi™ (adalimumab) should be carefully monitored. Imraldi should be discontinued if a patient develops a serious infection or sepsis. Appropriate therapy should be initiated until the infection is controlled. Physicians should exercise caution in patients with a history of recurrent infection and/or patients predisposed to infection.

See the full Summary of Product Characteristics for further information, including information relating to other opportunistic infections observed in patients receiving adalimumab.

Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.

Before initiation of therapy with Imraldi™ (adalimumab), all patients must be evaluated for both active or inactive (latent) tuberculosis infection. Evaluation should include a detailed medical assessment of patient history of tuberculosis or possible previous exposure to people with active tuberculosis and previous and/ or current immunosuppressive therapy.

Appropriate screening tests (i.e. tuberculin skin test and chest X-ray) should be performed in all patients (local recommendations may apply). It is recommended that the conduct and results of these tests are recorded in the Patient Reminder Card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.

lf active tuberculosis is diagnosed, Imraldi™ (adalimumab) therapy must not be initiated. lf latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted and appropriate treatment must be started with anti-tuberculosis prophylaxis treatment before the initiation of Imraldi™ (adalimumab). Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after therapy with Imraldi™ (adalimumab).

See the full Summary of Product Characteristics for further information on managing patients with suspected latent tuberculosis, patients with several or significant risk factors for tuberculosis, and patients with an indeterminate history of tuberculosis.

Reactivation of hepatitis B virus (HBV) has been observed in chronic carriers (i.e. surface antigen positive patients) receiving TNF-antagonists, including Imraldi™, with some cases having a fatal outcome.

Patients should be tested for HBV infection before initiating treatment with Imraldi™ (adalimumab) and, patients who test positive, consultation with a physician with expertise in the treatment of hepatitis B is recommended.

Carriers of HBV who require treatment with Imraldi™ (adalimumab) should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy.

ln patients who develop HBV reactivation, Imraldi™ (adalimumab) should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.

See the full Summary of Product Characteristics for further information.

TNF-antagonists, including adalimumab, have been associated in rare instances with new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome.

Prescribers should exercise caution in considering the use of Imraldi™ (adalimumab) in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of Imraldi™ (adalimumab) should be considered if any of these disorders develop.

See the full Summary of Product Characteristics for further information.

Serious allergic reactions associated with adalimumab were rare during clinical trials and non-serious allergic reactions associated with adalimumab were uncommon during clinical trials. However, reports of serious allergic reactions including anaphylaxis have been received following adalimumab administration.

lf an anaphylactic reaction or other serious allergic reaction occurs, administration of Imraldi™ (adalimumab) should be discontinued immediately and appropriate therapy initiated.

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients. However, the occurrence was rare.

In the post marketing setting, cases of leukaemia have been reported in patients treated with a TNF-antagonist.

Notwithstanding the increased background risk of lymphoma and leukaemia in patients with rheumatoid arthritis due to chronic inflammation, current knowledge would suggest that a possible risk for the development of lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be excluded.

See the full Summary of Product Characteristics for further information.

Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists. Adverse events of the haematologic system, including medically significant cytopenia (e.g. thrombocytopenia, leukopenia) have been reported with adalimumab.

All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on Imraldi™ (adalimumab) and discontinuation of Imraldi™ therapy should be considered in patients with confirmed significant haematologic abnormalities.

Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab.

lt is recommended that paediatric patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating adalimumab therapy.

Patients on adalimumab may receive concurrent vaccinations, except for live vaccines. Administration of live vaccines (e.g. Bacillus Calmette–Guérin (BCG) vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy.

In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also been reported in patients receiving adalimumab.

Imraldi™ (adalimumab) is contraindicated in moderate to severe heart failure and should be used with caution in patients with mild heart failure (NYHA class l/ll).

Treatment with Imraldi™ (adalimumab) must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.

Treatment with Imraldi™ (adalimumab) may result in the formation of autoimmune antibodies. The impact of long-term treatment with adalimumab on the development of autoimmune diseases is unknown.

If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Imraldi™ (adalimumab) and is positive for antibodies against double-stranded DNA, further treatment with Imraldi™ (adalimumab) should not be given. (see section 4.8 of the Summary of Product Characteristics).

Serious infections were seen in clinical studies with concurrent use of anakinra and another TNFantagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the combination of adalimumab and anakinra is not recommended. (See section 4.5 of the Summary of Product Characteristics).

Concomitant administration of adalimumab with other biological disease-modifying antirheumatic drugs (DMARDS) (e.g, anakinra and abatacept) or other TNF-antagonists is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions. (See section 4.5 of the Summary of Product Characteristics).

See the full Summary of Product Characteristics for further information.

There is limited safety experience of surgical procedures in patients treated with adalimumab. The long half-life of adalimumab should be taken into consideration if a surgical procedure is planned.

A patient who requires surgery while on Imraldi™ (adalimumab) should be closely monitored for infections, and appropriate actions should be taken.

There is limited safety experience in patients undergoing arthroplasty while receiving Imraldi™ (adalimumab).

Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture that may require surgical treatment. Available data suggest that adalimumab does not worsen or cause strictures.

The frequency of serious infections among adalimumab treated subjects over 65 years of age (3.7%) was higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome.

Particular attention regarding the risk for infection should be paid when treating the elderly.

See Vaccinations above.

This medicinal product contains 20 mg sorbitol in each pre-filled syringe/pre-filled pen.

Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.

This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially ‘sodium-free’.

Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant methotrexate.

Antibody formation was lower when adalimumab was given together with methotrexate in comparison with use as monotherapy. Administration of adalimumab without methotrexate resulted in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab. (see section 5.1 of the Summary of Product Characteristics).

See the full Summary of Product Characteristics for further information.

Concomitant administration of adalimumab with other TNF-antagonists is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions. (See section 4.4 of the Summary of Product Characteristics).

The combination of Imraldi™ (adalimumab) and anakinra is not recommended. (See section 4.4 of the Summary of Product Characteristics).

The combination of Imraldi™ (adalimumab) and abatacept is not recommended. (See section 4.4 of the Summary of Product Characteristics).

Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy and continue its use for at least five months after the last Imraldi™ treatment.

A large number (approximately 2,100) of prospectively collected pregnancies exposed to adalimumab resulting in live birth with known outcomes, including more than 1,500 exposed during the first trimester, does not indicate an increase in the rate of malformation in the newborn.

Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab during pregnancy. Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal immune responses in the newborn. Adalimumab should only be used during pregnancy if clearly needed.

See the full Summary of Product Characteristics for further information.

Limited information from the published literature indicates that adalimumab is excreted in breast milk at very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1 % to 1 % of the maternal serum level.

Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability.

No effects on the breastfed newborns/infants are anticipated. Consequently, adalimumab can be used during breastfeeding.

Preclinical data on fertility effects of adalimumab are not available.