Simponi

Antipsoriatic Monoclonal Antibodies and Others
Anti-Rheumatic Monoclonal Antibodies
Tumor Necrosis Factor (TNF)-Alpha Inhibitors

Visually inspect the solution for particulate matter or discoloration before administration.

Preparation of Intravenous infusion
Only the Simponi Aria formulation of golimumab may be administered intravenously.
The Simponi Aria injection solution in vials should be clear to slightly opalescent and colorless to light yellow. The solution may develop a few fine translucent particles, as golimumab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present.
Calculate the number of vials necessary based on the recommended dosage. Each vial contains 50 mg/4 mL of golimumab.
Do not shake the vials.
Dilute the total volume of golimumab with 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to yield a final volume of 100 mL for infusion. Withdraw the volume of diluent from a 100 mL infusion bag or bottle equal to the total volume of golimumab to be added. Slowly add golimumab to the diluent using aseptic technique and gently mix.
Discard any unused solution remaining in vials.
Storage: The prepared infusion solution may be stored for up to 4 hours at room temperature.
 
Intravenous infusion administration
Prior to intravenous infusion, visually inspect the diluted infusion solution for particulate matter or discoloration. Do not use if these exist.
Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).
Infuse over 30 minutes.
Do not infuse concomitantly in the same intravenous line with other agents. No physical biochemical compatibility studies have been conducted to evaluate the use of other intravenous agents in the same intravenous line.

Only the Simponi formulation of golimumab may be administered subcutaneously.
Simponi injection in prefilled syringes or the SmartJect Autoinjector is clear to slightly opalescent and colorless to light yellow. Do not use if the solution is discolored, or cloudy, or if foreign particles are present.
Do not shake the prefilled syringe or autoinjector.
Injection sites include the front part of the middle thigh and the lower abdomen (but do not inject within 2 inches of the navel). If administered by another person, the prefilled syringe may be given in the back of the upper arm; do not administer the autoinjector into the arms.
Rotate injection sites. Do not administer where skin is tender, bruised, red, or hard.
 
SmartJect Autoinjector
Allow the single-use prefilled autoinjector to reach room temperature by removing the product from the refrigerator and allow to sit at room temperature for at least 30 minutes before use. Do not warm the autoinjector in any other way (e.g., hot water or microwave).
Immediately before use, remove cap. Inject golimumab within 5 minutes of cap removal. Do not put the cap back on, as cap replacement may damage the needle. Do not inject if autoinjector has been dropped without the cap on.
Place the open end of the autoinjector against the injection site at a 90-degree angle. Make sure the green safety sleeve is flat against the skin and the injection site is as flat as possible; do not pinch the skin.
Push the autoinjector firmly against the skin until the green safety sleeve slides fully into the clear cover, then press the button. Listen for a loud first click; do not pull the autoinjector away from the skin. Wait for the second click. This usually takes 3 to 6 seconds but may take up to 15 seconds. If the autoinjector is pulled away from the skin before the injection is complete, the full dose may not be administered.
Do not rub the injection site.
Look at the viewing window. If it is not yellow, call 1-800-526-7736; do not administer a second dose without talking with the prescribing health care provider.
 
Prefilled syringe
Allow the single-use prefilled syringe to reach room temperature by removing the product from the refrigerator and allow to sit at room temperature for at least 30 minutes before use. Do not warm the autoinjector in any other way (e.g., hot water or microwave).
Immediately before use, remove the needle cover by pulling it straight off; do not twist off or recap. Inject golimumab within 5 minutes of needle cover removal.
Hold the syringe in one hand like a pencil and use the other hand to gently pinch a fold of skin at the cleaned injection site. Do not touch the plunger or the area above finger flange prior to administration as this may cause the needle safety device to activate.
Insert the needle at a 45-degree angle to the skin. Inject golimumab by pushing the plunger all the way down until it stops. Release pressure from the plunger. The safety guard will cover the needle and lock into place, removing the needle from the skin.
Do not rub the injection site.
Properly dispose of the used prefilled syringe.

vasculitis / Delayed / 0-1.0
hepatic failure / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

elevated hepatic enzymes / Delayed / 4.0-7.9
antibody formation / Delayed / 2.0-4.0
hypertension / Early / 3.0-3.0
psoriasis / Delayed / 0-1.0
neutropenia / Delayed / 0-1.0
leukopenia / Delayed / 1.0-1.0
constipation / Delayed / 0-1.0
hepatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
bullous rash / Early / Incidence not known
dyspnea / Early / Incidence not known

infection / Delayed / 12.0-28.0
injection site reaction / Rapid / 3.4-6.0
influenza / Delayed / 4.0-5.0
sinusitis / Delayed / 0-2.0
dizziness / Early / 0-2.0
paresthesias / Delayed / 0-2.0
fever / Early / 2.0-2.0
weakness / Early / Incidence not known
urticaria / Rapid / Incidence not known
nausea / Early / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known

Patients who receive golimumab or other TNF blockers are at increased risk for developing serious infections that may result in hospitalization and/or death. Patients with a history of recurrent infections with underlying conditions that may predispose them to infections (e.g., elderly and patients with advanced or uncontrolled diabetes mellitus, malignancy, bone marrow suppression, or immunosuppression) may not be appropriate candidates for treatment. Evaluate the risks and benefits before beginning golimumab therapy in patients with chronic or recurrent infections or in patients with underlying conditions predisposing them to infection. Do not administer golimumab to patients with a clinically important active infection like sepsis or influenza as host defenses will be affected. Most serious infections have occurred in patients receiving concurrent immunosuppressives such as methotrexate and corticosteroid therapy. Serious infections may involve multiple organ systems and include bacterial infection (Legionella and Listeria), mycobacterial infection (disseminated tuberculosis or extrapulmonary tuberculosis), fungal infection (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, listeriosis, Pneumocystis jiroveci pneumonia), parasitic infection, viral infection, and other opportunistic infections. Patients with invasive fungal infections (specifically histoplasmosis) may present with disseminated rather than localized disease. Health care providers should be aware that antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Carefully consider the risks before initiating therapy in patients who reside in histoplasmosis, blastomycosis, or coccidioidomycosis endemic zones. In patients who develop severe systemic illness, consider administering empiric antifungal therapy. Patients need to be evaluated for tuberculosis risk factors and for latent or active tuberculosis infection with a tuberculin skin test both before and during treatment. The possibility of anergy needs to be considered when interpreting the test result. If tuberculin skin testing is performed for latent tuberculosis infection, an induration size of 5 mm or greater should be considered positive even if the patient was vaccinated previously with Bacille Calmette-Guerin. Cases of tuberculosis have occurred and treatment of latent infection should be started before golimumab initiation. Treatment of latent tuberculosis in patients with a reactive tuberculin test reduces the risk of tuberculosis reactivation. Consider antituberculosis therapy before golimumab initiation in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and in patients who have several or highly significant risk factors for tuberculosis infection (e.g., close contact with infected persons or travel to endemic zones) and have a negative test for latent tuberculosis. Monitor all patients for signs and symptoms of tuberculosis including those who tested negative for latent tuberculosis infection prior to initiating golimumab, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection. Educate patients about the symptoms of infection, and closely monitor patients for signs and symptoms of an infection during and after treatment. Patients who develop a new infection during treatment should be closely monitored and evaluated for appropriate antimicrobial therapy. If a patient develops a serious infection or sepsis, discontinue golimumab. In addition, care should be taken when switching from one biologic product to another as overlapping biological activity may further increase the risk of infection. Health care providers are encouraged to report adverse events to the MedWatch Safety Information and Adverse Event Reporting Program by telephoning 1-800-332-1088 or by completing the form online.[35501] [45593] [55376]

Golimumab neutralizes the biological activity of TNF-alpha; therefore, golimumab may affect host defenses against neoplastic disease. Cases of new primary malignancy, some fatal, have been reported among children, adolescents, and young adults (initiation of therapy at 18 years of age or younger), who received treatment with drugs in the TNF-blocker class, of which golimumab is a member. Approximately 50% of these malignancy 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 pediatric patients. Leukemia, melanoma, and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including golimumab. Most 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. These cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports. Also, a greater portion of malignancies occurred in the TNF-blocker group as compared with the control group among patients at higher risk for malignancies such as patients with chronic obstructive pulmonary disease (COPD) or patients with Wegener’s granulomatosis treated with concomitant cyclophosphamide. Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported mostly in adolescent and young adult males with inflammatory bowel disease such as Crohn's disease or ulcerative colitis treated with TNF-blockers; almost all cases have occurred in patients who had received a TNF-blocker concomitantly with either azathioprine or 6-mercaptopurine (6-MP) at or before diagnosis. However, whether or not the occurrence of hepatosplenic T-cell lymphoma is related to a TNF blocker or to a TNF blocker in combination with these other immunosuppressants is unknown. As a risk for the development for hepatosplenic T-cell lymphoma cannot be excluded, carefully consider the potential risk of golimumab with either azathioprine or 6-MP. Screen all patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma such as those with long-standing ulcerative colitis or primary sclerosing cholangitis and those with a history of dysplasia or colon carcinoma for dysplasia at regular intervals before and during golimumab receipt. Screening includes colonoscopy and biopsies per local recommendations. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Consider the risks and benefits of golimumab before treatment initiation in patients with a known malignancy other than a successfully treated non-melanoma skin cancer. Consider also the risks and benefits of golimumab continuation in patients who develop a malignancy including newly diagnosed dysplasia. Use of golimumab by patients with malignancy risk factors, a malignancy history, or current malignancy may be unadvisable.

Simponi, SIMPONI ARIA

Rx

Parenteral TNF blocker
Used for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, and ulcerative colitis
Boxed warning highlights risk for serious infections and potential for malignancy

50 mg subcutaneously once monthly. Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or nonbiologic disease modifying antirheumatic drugs (DMARDs) may be continued during subcutaneous golimumab therapy. Subcutaneous golimumab has been evaluated in adult patients with moderately to severely active rheumatoid arthritis (RA) in 3 multicenter, randomized, double-blind, controlled trials (n = 1,542). In patients with active RA previously treated with 1 or more doses of a tumor necrosis factor (TNF)-blocker, a 20% improvement in the American College of Rheumatology (ACR20) score at week 14 (primary endpoint) was achieved in 40% of patients who received subcutaneous golimumab 50 mg plus methotrexate compared with 17% of patients who received placebo plus methotrexate. In patients with active RA despite a stable dose of at least 15 mg/week of methotrexate and who had not been previously treated with a biologic TNF-blocker, a 20% improvement in the ACR20 score at week 14 (primary endpoint) was reported in 55% of patients who received subcutaneous golimumab 50 mg plus methotrexate compared with 33% of patients who received methotrexate alone in another trial. In patients with active RA who had not previously received methotrexate or a biologic TNF-blocker, a 50% improvement in the American College of Rheumatology (ACR50) score at week 24 (primary endpoint) occurred in 40% of patients who received subcutaneous golimumab 50 mg plus methotrexate (up to 20 mg/week) compared with 29% of patients who received methotrexate alone in a third trial. Clinical practice guidelines recommend a TNF blocker +/- methotrexate as an option for patients with a disease duration of less than 6 months and high disease activity with poor prognostic feature presence. For established disease, adding or switching to an anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. A switch to a different anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to an anti-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of a non-TNF biologic or with a serious or non-serious adverse event to the drug. The goal is low disease activity or remission.

2 mg/kg/dose IV every 4 weeks for 2 doses, then 2 mg/kg/dose IV every 8 weeks. Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), non-biologic disease modifying antirheumatic drugs (DMARDs), and/or analgesics may be continued during IV golimumab therapy. In patients with active rheumatoid arthritis despite 3 months or more of methotrexate therapy, a 20% improvement in the American College of Rheumatology (ACR20) score at week 14 (primary endpoint) was achieved in 58.5% of patients who received IV golimumab plus methotrexate compared with 24.9% of patients who received placebo plus methotrexate (p less than 0.001, GO-FURTHER trial). Patients were permitted to receive standard prophylaxis for infusion reactions (e.g., acetaminophen, antihistamines) but not corticosteroids. A significant difference in ACR20 response was observed by week 2. Additionally, a good or moderate European League Against Rheumatism (EULAR) response was achieved at week 14 in significantly more patients who received IV golimumab compared with placebo (81.3% vs. 40.1%; p less than 0.001). In this same trial, patients receiving golimumab plus methotrexate demonstrated greater improvement from baseline compared to placebo plus methotrexate in the physical component summary, mental component summary scores, and in all 8 domains of the Short Form Health Survey (SF-36).

50 mg subcutaneously once per month. May be used alone or in combination with methotrexate or other non-biologic DMARDs. Corticosteroids, NSAIDs, and/or analgesics may be continued during golimumab receipt.

2 mg/kg IV over 30 minutes. Repeat this dose 4 weeks later and then administer every 8 weeks thereafter.

50 mg subcutaneously once per month. May be used alone or in combination with methotrexate or other non-biologic DMARDs. Corticosteroids, NSAIDs, and/or analgesics may be continued during golimumab receipt.[35501] In a study in patients with psoriatic arthritis, 51% of 146 recipients of golimumab 50 mg subcutaneously every 4 weeks had an ACR20 at week 14 as compared with 9% of 113 placebo recipients, and 40% of golimumab recipients had at least a 75% improvement in the Psoriasis Area and Severity Index (PASI) criteria as compared with 2.5% of placebo recipients. Further, a median 25% improvement in the Nail Psoriasis Severity Index score was noted for golimumab recipients; no change was noted for placebo recipients.[35504]

2 mg/kg/dose IV at weeks 0 and 4, then every 8 weeks thereafter.

80 mg/m2/dose IV at weeks 0 and 4, then every 8 weeks thereafter.

80 mg/m2/dose IV at weeks 0 and 4, then every 8 weeks thereafter.[55376]

200 mg subcutaneously at week 0, then 100 mg subcutaneously at week 2, then 100 mg subcutaneously every 4 weeks. Guidelines strongly recommend golimumab for induction of remission in persons with moderately to severely active ulcerative colitis and for maintenance of remission in persons who respond to golimumab induction. 

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Adalimumab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Anakinra: (Major) Avoid the concomitant use of anakinra with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection with no additional clinical benefit. Data suggest a higher rate of serious infections when anakinra and a TNF inhibitor is used in combination with anakinra compared with either drug given alone. Neutropenia (1,000/mcL or less) was observed in 2% of patients receiving the combination. The use of anakinra with a TNF inhibitor in combination did not yield any additional clinical benefit as compared to the use of the TNF inhibitor alone.
Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Antithymocyte Globulin: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Azathioprine: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Basiliximab: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Canakinumab: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Certolizumab pegol: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including golimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with golimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclosporine: (Moderate) If golimumab is initiated or discontinued in a patient taking cyclosporine, monitor the cyclosporine concentration; cyclosporine dose adjustment may be needed. Monitor closely for additive immunosuppression and for infection. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine.
Etanercept: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including etanercept, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with etanercept. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Infliximab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including infliximab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with infliximab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Live Vaccines: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Methotrexate: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Methylprednisolone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with tumor necrosis factor (TNF) modifiers. Coadministration may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic TNF-modifier therapy should not be treated with natalizumab.
Prednisolone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Prednisone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Rilonacept: (Contraindicated) Concurrent use of rilonacept and tumor necrosis factor (TNF) modifiers is not advised, as the risk of serious infections may be increased. Although concurrent use has not been evaluated in clinical trials, an increased incidence of serious infections and neutropenia has been associated with administration of another drug that blocks IL-1 in combination with TNF inhibitors.
Rituximab: (Major) Avoid the concomitant use of rituximab with golimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab with golimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Theophylline, Aminophylline: (Moderate) If golimumab is initiated or discontinued in a patient taking aminophylline, monitor the theophylline concentration; aminophylline dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as aminophylline. (Moderate) If golimumab is initiated or discontinued in a patient taking theophylline, monitor the theophylline concentration; theophylline dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as theophylline.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vedolizumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Warfarin: (Moderate) If golimumab is initiated or discontinued in a patient taking warfarin, monitor the INR; warfarin dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as warfarin, and alter the clinical response to warfarin treatment.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

SIMPONI ARIA Intravenous Inj Sol: 4mL, 50mg
Simponi Subcutaneous Inj Sol: 0.5mL, 1mL, 50mg, 100mg

50 mg/dose subcutaneously for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 2 mg/kg/dose IV for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 200 mg/dose subcutaneously for ulcerative colitis induction and 100 mg/dose subcutaneously for ulcerative colitis maintenance.

50 mg/dose subcutaneously for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 2 mg/kg/dose IV for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 200 mg/dose subcutaneously for ulcerative colitis induction and 100 mg/dose subcutaneously for ulcerative colitis maintenance.

80 mg/m2/dose IV for polyarticular juvenile idiopathic arthritis and psoriatic arthritis.

2 to 12 years: 80 mg/m2/dose IV for polyarticular juvenile idiopathic arthritis and psoriatic arthritis.
1 year: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Golimumab neutralizes the biological activity of tumor necrosis factor (TNF)-alpha by binding to it and blocking its interaction with cell surface TNF receptors. Golimumab binds to both the soluble and the transmembrane bioactive forms of human TNF-alpha. Golimumab does not bind to or inactivate lymphotoxin (TNF-beta), which is a related cytokine that utilizes the same receptors as TNF-alpha. Elevated TNF-alpha concentrations in the blood, synovium, and joints have been implicated in the pathophysiology of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Tumor necrosis factor-alpha is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Biological activities attributed to TNF-alpha include induction of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, G-CSF, and GM-CSF; enhancement of leukocyte migration by increasing endothelial layer permeability; expression of adhesion molecules responsible for leukocyte infiltration such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by endothelial cells and leukocytes; activation of neutrophil and eosinophil functional activity; proliferation of fibroblasts; inhibition of osteoblast differentiation; upregulation of Fas-mediated apoptosis of osteoblasts; synthesis of prostaglandins; indirect induction of osteoclast differentiation and bone resorption; and induction of acute phase and other liver proteins. Activated macrophages release TNF-alpha, which acts on chondrocytes, fibroblasts, and osteoclasts to release metalloproteinases (MMP) and other effector molecules that induce the migration of polymorphonuclear cells.
 
Golimumab receipt to adults with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis was associated with reductions in C-reactive protein, IL-6, matrix MMP-3, ICAM-1, and vascular endothelial growth factor concentrations.

Golimumab is administered subcutaneously or intravenously. The mean Vd is 115 mL/kg in healthy subjects and 151 mL/kg in patients with rheumatoid arthritis (RA), indicating the drug is primarily distributed in the circulatory system with limited extravascular distribution. The exact metabolic pathway of the drug is not known. The median terminal half-life of subcutaneous golimumab was estimated to be approximately 2 weeks among patients with active RA, ankylosing spondylitis, or psoriatic arthritis and the mean terminal half-life of intravenous golimumab was 14 +/- 4 days in patients with RA.[55376] [35501]
 
Affected cytochrome P450 isoenzymes and drug transporters: Unknown
The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines during chronic inflammation. It is expected that golimumab may normalize the formation of CYP450 enzymes during treatment. Upon initiation or discontinuation of golimumab in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.[55376] [35501]

A mean Cmax of 44.4 +/- 11.3 mcg/mL occurred after IV administration of a 2 mg/kg dose in patients with rheumatoid arthritis. Steady-state serum concentrations were reached by week 12 when 2 mg/kg was given to patients with rheumatoid arthritis at weeks 0, 4, and every 8 weeks thereafter.[55376]

Steady-state concentrations were attained by week 12 with receipt of 50 mg subcutaneously every 4 weeks in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Patients who developed anti-golimumab antibodies generally had lower steady-state serum trough concentrations. In contrast, higher mean steady-state trough concentrations were obtained among patients who also took methotrexate. Specifically, as compared to patients taking golimumab without methotrexate, the mean steady-state trough concentration was 52% higher, 36% higher, and 21% higher in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, respectively, that were taking golimumab plus methotrexate. In patients with ulcerative colitis, steady-state concentrations were attained by week 8 after receipt of 200 mg and 100 mg at week 0 and 2, followed by 100 mg every 4 weeks.

There are no adequate and well-controlled trials of golimumab in pregnant women; use during pregnancy should be balanced with the risks and benefits of continuing therapy for the individual patient versus the risks posed by uncontrolled disease or disease flares. Experts and guidelines recommend that golimumab may be continued during pregnancy, as cohort and registry monitoring data for TNF-blocker therapy during pregnancy have not revealed an increase in adverse fetal outcomes. Golimumab is transported across the placenta and may affect immune response in the in utero exposed infant. To minimize drug transfer at birth, it is recommended to administer the final golimumab dose 4 to 6 weeks prior to anticipated delivery, then resume the drug postpartum. Neonates and infants born to women treated with TNF-blockers during their pregnancy may be at increased risk of infection for up to 6 months, and administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months after the mother's last injection during pregnancy. In embryo-fetal toxicology studies involving pregnant cynomolgus monkeys with doses that produced golimumab exposures approximately 360 times greater than the maximum recommended human dose (MRHD) for subcutaneous administration and 200 times the MRHD for intravenous administration, no evidence of maternal or fetal harm was noted.