WARNING: SERIOUS INFECTIONS and MALIGNANCY
SERIOUS INFECTIONS
Patients treated with adalimumab products, including SIMLANDI, are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue SIMLANDI 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 pulmonary or extrapulmonary disease. Evaluate patients for tuberculosis risk factors and test for latent TB before initiating SIMLANDI and periodically during therapy. Initiate treatment for latent TB prior to SIMLANDI 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 SIMLANDI prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with SIMLANDI, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
- Do not start SIMLANDI during an active infection, including localized infections.
- Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants, may be at greater risk of infection.
- If an infection develops, monitor carefully and initiate appropriate therapy.
- Drug interactions with biologic products: A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of SIMLANDI with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.
MALIGNANCY
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. Postmarketing 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 products. 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.
- Consider the risks and benefits of TNF blocker-treatment, including SIMLANDI, prior to initiating therapy in patients with known malignancy.
- Non-melanoma skin cancer (NMSC) was reported during clinical trials for adalimumab-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy for the presence of NMSC prior to and during treatment with SIMLANDI.
- In the adalimumab clinical trials there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk than the general population for the development of lymphoma, even in the absence of TNF blockers.
- Postmarketing cases of acute and chronic leukemia have been reported in association with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases represented a variety of different malignancies and included rare malignancies associated with immunosuppression and malignancies that are not usually observed in children and adolescents.
Hypersensitivity Reactions
Anaphylaxis or serious allergic reactions have been reported following administration of adalimumab products. If an anaphylactic or other serious hypersensitivity reaction occurs, immediately discontinue administration of SIMLANDI and institute appropriate therapy.
Hepatitis B Virus Reactivation
- Use of TNF blockers, including SIMLANDI, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases with HBV reactivation occurring in conjunction with TNF blocker therapy have been fatal.
- Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
- Exercise caution in patients identified as carriers of HBV and closely monitor during and after SIMLANDI treatment.
- In patients who develop HBV reactivation, stop SIMLANDI and initiate effective anti-viral therapy. Exercise caution when resuming SIMLANDI after HBV treatment.
Neurologic Reactions
- Use of TNF blocking agents, including adalimumab products, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating disease, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.
- Exercise caution when considering SIMLANDI for patients with these disorders; discontinuation of SIMLANDI should be considered if any of these disorders develop.
- There is a known association between intermediate uveitis and central demyelinating disorders.
Hematological Reactions
- Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blocking agents. Medically significant cytopenia has been infrequently reported with adalimumab products.
- Advise patients to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor).
- Consider stopping SIMLANDI if significant hematologic abnormalities occur.
Heart Failure
Worsening and new onset congestive heart failure (CHF) have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products; exercise caution when using SIMLANDI in patients who have heart failure and monitor them carefully.
Autoimmunity
Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
Immunizations
- Patients on SIMLANDI should not receive live vaccines.
- Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating SIMLANDI therapy.
- Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab products in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.
ADVERSE REACTIONS
The most common adverse reactions (greater than or equal to 10%): are infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.
SIMLANDI® (adalimumab-ryvk) injection, is a tumor necrosis factor (TNF)-blocker indicated for:
- Rheumatoid Arthritis (RA): Alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs), for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA.
- Juvenile Idiopathic Arthritis (JIA): Alone or in combination with methotrexate for reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older.
- Psoriatic Arthritis (PsA): Alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA.
- Ankylosing Spondylitis (AS): Reducing signs and symptoms in adult patients with active AS.
- Crohn’s Disease (CD): Treatment of moderately to severely active CD in adults and pediatric patients 6 years of age and older.
- Ulcerative Colitis (UC): Treatment of moderately to severely active UC in adult patients.
- Limitations of use: The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers.
- Plaque Psoriasis (Ps): The treatment of adult patients with moderate to severe chronic Ps who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. SIMLANDI should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
- Hidradenitis Suppurativa (HS): The treatment of moderate to severe HS in adult patients.
- Uveitis: The treatment of non-infectious intermediate, posterior, and panuveitis in adult patients.
To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for SIMLANDI, including BOXED WARNINGS.
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