Simponi Special Precautions

Infections: Bacterial (including sepsis and pneumonia), mycobacterial (tuberculosis), invasive fungal and opportunistic infections, including fatalities, have been reported in patients receiving TNF-blocking agents, including golimumab. Patients have frequently presented with disseminated rather than localized disease. Some of these serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections.
SIMPONI should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of SIMPONI in patients with a chronic infection or a history of recurrent infection. Patients should be advised of and avoid exposure to potential risk factors for infection as appropriate.
Patients must be monitored closely for infections including tuberculosis before, during and after treatment with golimumab. Because the elimination of golimumab may take up to 5 months, monitoring should be continued throughout this period. Further treatment with SIMPONI must not be given if a patient develops a serious infection or sepsis.
Tuberculosis: Patients should be evaluated for tuberculosis risk factors (including close contact with a person with active tuberculosis) and tested for latent tuberculosis infections prior to treatment with SIMPONI. Treatment of latent tuberculosis infections should be initiated prior to therapy with SIMPONI.
Anti-tuberculosis therapy should be considered prior to initiation of SIMPONI in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Tests for latent tuberculosis may yield false negative results, especially in patients who are immunocompromised or severely ill. Prior to initiating SIMPONI, treatment for latent TB should be considered in patients who have significant risk factors for TB despite a negative test for latent tuberculosis. The decision to initiate anti-tuberculosis therapy in these patients should only be made following consultation with a physician with expertise in the treatment of tuberculosis and taking into account both the risk for latent tuberculosis infection and the risks of anti-tuberculosis therapy.
In patients receiving SIMPONI, tuberculosis has frequently presented as disseminated or extrapulmonary disease. Cases of active tuberculosis have occurred in patients treated with SIMPONI during and after treatment for latent tuberculosis. Patients receiving SIMPONI should be monitored closely for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.
Opportunistic Infections: Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease.
For patients who have resided in or travelled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of SIMPONI treatment should be carefully considered before initiation or continuation of SIMPONI therapy.
In at-risk patients treated with SIMPONI, an invasive fungal infection should be suspected if they develop a serious systemic illness. Invasive fungal infections may present as disseminated rather than localized disease, and antigen and antibody testing may be negative in some patients with active infection. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. The decision to administer empiric antifungal therapy should be made, if feasible, in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy.
Hepatitis B Virus (HBV) Reactivation: As observed with the use of other immunosuppressive drugs, the use of TNF-blocking agents, including golimumab has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of the virus (i.e., surface antigen positive). In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants. Patients should be tested for HBV infection before initiating treatment with immunosuppressants, including SIMPONI. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Chronic carriers of hepatitis B should be appropriately evaluated and monitored prior to the initiation of, during treatment with, and for several months following discontinuation of SIMPONI.
Malignancies: The potential role of TNF-blocking therapy in the development of malignancies is not known. Caution should be exercised when considering TNF-blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.
Pediatric Malignancy: Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤18 years of age), of which golimumab is a member. Approximately half of the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression, and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF-blocker therapy. Most of the patients were receiving concomitant immunosuppressants, such as methotrexate, azathioprine, or 6-mercaptopurine. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous post-marketing reports.
Lymphoma: In the controlled portions of clinical trials of all the TNF-blocking agents including SIMPONI, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with control patients. During the SIMPONI Phase 2 and Phase 3 clinical trials in RA, PsA and AS, the incidence of lymphoma in SIMPONI-treated patients was higher than expected in the general population. Patients with rheumatoid arthritis and other chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy.
Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Nearly all of these cases have occurred in patients with Crohn's disease or ulcerative colitis. The majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6-MP) concomitantly with a TNF-blocker at or prior to diagnosis. The potential risk with the combination of AZA or 6-MP and SIMPONI should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF-blockers cannot be excluded.
Leukemia: Cases of acute and chronic leukemia have been reported with TNF-blocker use, including SIMPONI, in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately two-fold) than the general population for the development of leukemia.
Non-lymphoma Malignancy: In the controlled portions of the SIMPONI Phase 2 and Phase 3 clinical trials in RA, PsA, AS, and UC, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the SIMPONI and the control groups.
In an exploratory clinical trial evaluating the use of SIMPONI in patients with severe persistent asthma, more patients treated with SIMPONI reported malignancies compared with control patients. The significance of this finding is unknown.
Colon Dysplasia/Carcinoma: It is not known if SIMPONI treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated with SIMPONI, the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued.
Skin Cancers: Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including golimumab (see Post-Market Adverse Drug Reactions under Adverse Reactions). Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
Cardiovascular: Congestive Heart Failure (CHF): Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including golimumab. Some cases had a fatal outcome. Cases of CHF in patients with known cardiovascular risk factors have been observed with SIMPONI. In several exploratory trials of other TNF-blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. SIMPONI has not been studied in patients with CHF. SIMPONI should be used with caution in patients with heart failure. If a decision is made to administer SIMPONI to patients with heart failure, they should be closely monitored during therapy, and SIMPONI should be discontinued if new or worsening symptoms of heart failure appear.
Concurrent Administration with Anakinra: Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF-blocking agent, etanercept, with an increased risk of neutropenia and no added clinical benefit. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the combination of anakinra and other TNF-blocking agents. Therefore, the combination of SIMPONI and anakinra is not recommended (see Drug-Drug Interactions under Interactions).
Concurrent Administration with Abatacept: In clinical studies, concurrent administration of TNF-blocking agents and abatacept have been associated with an increased risk of infections including serious infections compared with TNF-blocking agents alone, without increased clinical benefit. Because of the nature of the adverse events seen with the combination of TNF-blocking agents and abatacept therapy, the combination of SIMPONI and abatacept is not recommended (see Drug-Drug Interactions under Interactions).
Concurrent Administration with other Biological Therapeutics: There is insufficient information regarding the concomitant use of golimumab with other biological therapeutics used to treat the same conditions as SIMPONI. The concomitant use of SIMPONI with these biologics is not recommended because of the possibility of an increased risk of infection.
Switching between Biological Therapeutics: When switching from one biologic to another, patients should continue to be monitored, since overlapping biological activity may further increase the risk of infection.
Hematologic Reactions: There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia and thrombocytopenia in patients receiving TNF-blockers, including golimumab. In clinical studies, cases of pancytopenia, leukopenia, neutropenia and thrombocytopenia have occurred in SIMPONI I.V.-treated patients. Caution should be exercised in patients treated with SIMPONI who have a current or past history of significant cytopenias. 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). Discontinuation of SIMPONI therapy should be considered in patients with confirmed significant hematologic abnormalities.
Immune: Immunosuppression: The possibility exists for TNF-blocking agents, including golimumab, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses. In Phase 1 RA studies, in 81 patients evaluated, there were no substantial differences between subjects receiving SIMPONI and placebo with respect to responses to delayed-type hypersensitivity antigens. The impact of treatment with golimumab on the development and course of malignancies, as well as active and/or chronic infections, is not fully understood (see as previously mentioned and Adverse Reactions).
Immunizations: Live Vaccines/Therapeutic Infectious Agents: Patients treated with SIMPONI may receive concurrent vaccinations, except for live vaccines.
In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections. It is recommended that live vaccines not be given concurrently with SIMPONI.
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with SIMPONI.
Non-live Vaccines: Psoriatic arthritis patients treated with SIMPONI in one Phase 3 PsA study were able to mount effective B-cell immune responses to pneumococcal polysaccharide vaccine. Similar numbers of psoriatic arthritis patients receiving SIMPONI and not receiving SIMPONI had at least a two-fold increase in antibody titers. The proportions of patients with response to pneumococcal vaccine were lower among SIMPONI and control-treated patients receiving MTX compared with patients not receiving MTX. Overall, the data indicate that SIMPONI does not suppress the humoral immune response to this vaccine.
Allergic Reactions: Hypersensitivity Reactions: Allergic reactions (e.g., rash, urticaria, and rarely anaphylaxis and serum sickness-like reactions) have been observed in patients treated with TNF-blocking agents. In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following SIMPONI administration. Some of these reactions occurred after the first administration of SIMPONI. If any serious allergic or anaphylactic reaction occurs, administration of SIMPONI should be discontinued immediately and appropriate therapy initiated.
Latex Sensitivity: The needle cover on the pre-filled syringe as well as the pre-filled syringe in the autoinjector contains dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex.
Autoimmune Processes: Treatment with TNF-blockers, including golimumab may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms of a lupus-like syndrome following treatment with SIMPONI, treatment should be discontinued (see Clinical Trial Adverse Drug Reactions: Immune: Autoantibodies under Adverse Reactions).
Autoimmune hepatitis has been reported for other members of the anti-TNFα class.
Demyelinating Disorders: Use of TNF-blocking agents, of which golimumab is a member, have been associated with cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS), optic neuritis and peripheral demyelinating disorders, including Guillain-Barré syndrome. In clinical trials, cases of central demyelination, MS, and peripheral demyelinating polyneuropathy have been reported in patients treated with SIMPONI. Prescribers should exercise caution in considering the use of TNF-blockers, including SIMPONI, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of SIMPONI should be considered if these disorders develop.
Sexual Function/Reproduction: It is not known whether golimumab can impair fertility in humans. No impairment of fertility was observed in a fertility and general reproduction toxicity study conducted in mice using the analogous anti-mouse TNFα antibody.
Surgery: There is limited safety experience of SIMPONI treatment in patients who have undergone surgical procedures, including arthroplasty. The long half-life should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on SIMPONI should be closely monitored for infections, and appropriate actions should be taken.
Women of Childbearing Potential: Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last golimumab treatment.
Renally and Hepatically Impaired: Specific studies of SIMPONI have not been conducted in these patient populations. SIMPONI should be used with caution in subject with impaired hepatic function.
Monitoring and Laboratory Tests: There is no known interference between SIMPONI and laboratory tests.
Potential for Medication Errors: SIMPONI is registered in 50 mg strength for subcutaneous administration. It is important that the right strength is used to administer the correct dose as indicated in Dosage & Administration. Care should be taken to provide the right strength to ensure that patients are not underdosed or overdosed.
Effects on Ability to Drive and Use Machines: No studies on the effect on the ability to drive and use machines have been performed. SIMPONI may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of SIMPONI.
Use in Pregnancy: See Pregnant Women under Use in Pregnancy & Lactation.
Use in Lactation: See Nursing Women under Use in Pregnancy & Lactation.
Use in Children: The safety and efficacy of SIMPONI have not been established in pediatric patients aged 17 years and younger.
Use in the Elderly: In the Phase 3 SIMPONI trials in RA, PsA, and AS, no overall differences in AEs, SAEs, and serious infections in patients age 65 or older who received SIMPONI were observed compared with younger patients. In UC, there were insufficient numbers of patients aged 65 and over to determine whether they respond differently from patients aged 18 to 65. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly. There were no patients aged 65 and over in the nr-Ax SpA trial.