Golimumab

Class: Disease-modifying Antirheumatic Agents
VA Class: MS190
Chemical Name: Disulfide with human monoclonal CNTO 148 k-chain anti-(human tumor necrosis factor a) (human monoclonal CNTO 148 g1-chain) immunoglobulin G1 dimer.
Molecular Formula: C₆₅₃₀H₁₀₀₆₈N₁₇₅₂O₂₀₂₆S₄₄
CAS Number: 476187-74-5
Brands: Simponi

Special Alerts:

[Posted 09/07/2011] ISSUE: FDA notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNF) blockers has been updated to include the risk of infection from two bacterial pathogens, Legionella and Listeria. In addition, the Boxed Warning and Warnings and Precautions sections of the labels for all of the TNF blockers have been revised so that they contain consistent information about the risk for serious infections and the associated disease-causing pathogens.

Patients treated with TNF blockers are at increased risk for developing serious infections involving multiple organ systems and sites that may lead to hospitalization or death due to bacterial, mycobacterial, fungal, viral, parasitic, and other opportunistic pathogens.

BACKGROUND: The class of TNF blockers are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis.

RECOMMENDATION: The risks and the benefits of TNF blockers should be considered prior to initiating therapy in patients with chronic or recurrent infection and patients with underlying conditions that may predispose them to infection. See the Drug Safety Communication for a listing of recommendations for healthcare professionals and patients, as well as a data summary. For more information visit the FDA website at: and .

[Posted 04/14/2011] ISSUE: FDA continues to receive reports of a rare cancer of white blood cells (known as Hepatosplenic T-Cell Lymphoma or HSTCL, primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factors (TNF) blockers, as well as with azathioprine, and/or mercaptopurine. TNF blockers include infliximab (Remicade), etancercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).

BACKGROUND: HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.

Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.

• 
  

  Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

  
  


• 
  

  Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.

  
  


• 
  

  Know that people with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or meracaptopurine.

  
  

Read the Drug Safety Communications for other specific recommendations for Healthcare Professionals and Patients and the Data Summary for additional information. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for golimumab to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Serious Infections


• 
  

  Serious, sometimes fatal infections including tuberculosis (frequently disseminated or extrapulmonary), bacterial and viral infections, invasive fungal infections (may be disseminated), and other opportunistic infections reported.¹ (See Infectious Complications under Cautions.)

  
  


• 
  

  Carefully consider risks and benefits prior to initiating golimumab therapy in patients with chronic or recurring infections.¹

  
  


• 
  

  Evaluate patients for latent tuberculosis infection prior to and periodically during golimumab therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating golimumab therapy.¹

  
  


• 
  

  Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.¹ Discontinue golimumab if serious infection occurs.¹ Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.¹

  
  

• Malignancy


• 
  

  Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.¹ (See Malignancies and Lymphoproliferative Disorders under Cautions.)

  
  

Introduction

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a human immunoglobulin G₁ kappa (IgG₁) monoclonal antibody specific for human tumor necrosis factor (TNF; TNF-α).^{1 2 3 4 5 6 13 14 15}

Uses for Golimumab

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Rheumatoid Arthritis in Adults

Used in conjunction with methotrexate for the management of moderately to severely active rheumatoid arthritis in adults.^{1 2 3 4 17}

Psoriatic Arthritis

Used alone or in conjunction with methotrexate for the management of active psoriatic arthritis in adults.^{1 5}

Ankylosing Spondylitis

Used for the management of ankylosing spondylitis in adults with active disease.^{1 6}

Golimumab Dosage and Administration

General

Concomitant Therapy

• 
  

  Used in conjunction with methotrexate for the management of moderately to severely active rheumatoid arthritis in adults; may be used with or without methotrexate for management of psoriatic arthritis or ankylosing spondylitis in adults.¹

  
  


• 
  

  Corticosteroids, other nonbiologic DMARDs, and NSAIAs may be continued in adults receiving golimumab for the management of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

  
  

REMS Program

• 
  

  FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for golimumab.¹²

  
  


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  The program consists of a medication guide that must be provided to patients (see Advice to Patients) and a communication plan that includes initial communications targeting selected groups of clinicians.¹²

  
  


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  The goals are to inform patients about the serious risks associated with the drug and to inform clinicians about invasive fungal infections associated with use of TNF blocking agents (see Warnings/Precautions under Cautions).¹²

  
  

Administration

Sub-Q Administration

Administer by sub-Q injection into the thigh, lower abdomen, or upper arm; do not make abdominal injections within 2 inches of the umbilicus.¹ Use thigh (the preferred site) or abdomen for self-administration; may use upper arm if not self-administered.¹ Rotate injection sites.¹ Do not make injections into areas where the skin is tender, bruised, red, or hard or into scars or stretch marks.¹

Allow golimumab prefilled syringe or auto-injector to sit at room temperature outside of the carton for 30 minutes prior to injection; do not warm the drug in any other way (e.g., microwave, hot water).¹ Do not remove the syringe needle cover or auto-injector cap while the drug is warming to room temperature.¹

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training.¹

Dosage

Adults

Rheumatoid Arthritis

Sub-Q

50 mg once monthly.¹

Psoriatic Arthritis

Sub-Q

50 mg once monthly.¹

Ankylosing Spondylitis

Sub-Q

50 mg once monthly.¹

Special Populations

Dosage adjustment based on weight or gender not necessary.^{1 15} (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Renal Impairment

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Cautions for Golimumab

Contraindications

• 
  

  Manufacturer states none known.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Infectious Complications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, protozoal, and other opportunistic infections) reported with golimumab or other TNF blocking agents, particularly in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids).^{1 9} The most common opportunistic infections include tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis.¹ Infections frequently are disseminated.¹

Do not initiate golimumab in patients with active infections, including clinically important localized infections.¹ Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, and blastomycosis are endemic.¹

Closely monitor patients during and after golimumab therapy for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).^{1 9}

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.^{1 9} Discontinue golimumab if serious infection, opportunistic infection, or sepsis develops.^{1 9}

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.¹ When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to golimumab therapy.¹ Also consider antimycobacterial therapy prior to golimumab therapy for individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and for individuals with a negative tuberculin skin test who have risk factors for tuberculosis.¹ Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.¹

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.¹ Strongly consider tuberculosis in patients who develop new infections while receiving golimumab, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.¹

Invasive fungal infections often not recognized in patients receiving TNF blocking agents; this has led to delays in appropriate treatment.⁹

Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.^{1 9} Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.^{1 9}

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.⁹ Whenever feasible, consult specialist in fungal infections.⁹

Increased incidence of serious infection and neutropenia observed with concomitant use of etanercept (another TNF blocking agent) and anakinra (a human interleukin-1 receptor antagonist).^{1 10} (See Specific Drugs under Interactions.)

Increased incidence of infection and serious infection reported with concomitant use of a TNF blocking agent and abatacept.^{1 11} (See Specific Drugs under Interactions.)

Hepatitis B Virus (HBV) Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of this virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).¹ Death reported in a few individuals.¹ Use of multiple immunosuppressive agents may contribute to HBV reactivation.¹

Screen at-risk patients prior to initiation of therapy.¹ Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.¹ Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.¹ Discontinue golimumab and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.¹ Not known whether golimumab can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.¹

Malignancies and Lymphoproliferative Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.^{1 8} Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).^{1 8} Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.¹ FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.⁸

In controlled studies, lymphoma was reported more frequently in patients receiving golimumab or other TNF blocking agents than in control patients.¹ Patients with rheumatoid arthritis and other chronic inflammatory diseases, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma.¹

In clinical studies of golimumab, the rate of malignancies other than lymphoma was not increased in golimumab-treated patients compared with placebo recipients; the rate was similar to the expected rate in the general US population.¹

However, acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.^{1 8} Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.⁸ FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.^{1 8}

In other populations at increased risk for malignancies (e.g., patients with COPD, patients with Wegener’s granulomatosis receiving concomitant cyclophosphamide), a greater proportion of malignancies occurred in patients receiving TNF blocking agents compared with control patients.¹

Malignancies also reported in a limited number of patients with uncontrolled, severe persistent asthma† who received golimumab; not reported in control patients.^{1 16}

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.⁸ Consider risks and benefits of TNF blocking agents, including golimumab, before initiating therapy in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer) or when considering whether to continue therapy in patients who develop a malignancy.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic reactions not reported in patients who received golimumab in clinical studies.¹

Latex Sensitivity

The needle cover of the prefilled syringe and the syringe in the auto-injector contain dry natural rubber and should not be handled by individuals sensitive to latex.¹

Other Warnings/Precautions

Cardiovascular Effects

Worsening CHF and new-onset CHF reported in patients receiving TNF blocking agents; golimumab not studied in patients with history of CHF.¹ If used in patients with CHF, caution and careful monitoring recommended.¹ Discontinue therapy if new or worsening symptoms of heart failure occur.¹

Nervous System Effects

New onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis, reported in patients receiving TNF blocking agents; golimumab not studied in patients with multiple sclerosis.¹

Exercise caution when considering golimumab therapy in patients with CNS demyelinating disorders, including multiple sclerosis.¹

Hematologic Effects

Pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia reported during postmarketing surveillance in patients receiving TNF blocking agents.¹ Severe cytopenias not observed in clinical studies of golimumab; however, use with caution in patients who have substantial cytopenias.¹

Immunization

Patients may receive inactivated vaccines.¹ Avoid live vaccines.¹ (See Interactions.)

Immunologic Reactions and Antibody Formation

Formation of autoimmue antibodies and, rarely, development of a lupus-like syndrome reported with TNF blocking agents.¹ Golimumab not associated with development of antibodies to double-stranded DNA (anti-dsDNA) in clinical studies to date in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Antibodies to golimumab may develop.¹ However, the relationship between antibodies to the drug and efficacy or safety is not fully elucidated.¹

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including golimumab, particularly in patients receiving other immunosuppressive agents (e.g., corticosteroids, methotrexate) concomitantly.^{1 8} Onset of new cases observed weeks to years following initiation of drug.⁸ Some patients required hospitalization.^{1 8} Most patients experienced improvement following discontinuance of the TNF blocking agent.^{1 8} Recurrences reported upon rechallenge with a different TNF blocking agent.¹ FDA has concluded that there is a possible association between use of TNF blocking agents and development of psoriasis.⁸

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.⁸ Consider discontinuance of golimumab if psoriasis is severe or if it worsens or does not improve despite topical treatment.¹

Hepatic Effects

Severe hepatic reactions, including acute liver failure, reported in patients receiving TNF blocking agents.¹

Increased serum ALT and AST concentrations reported in patients receiving golimumab.¹ Relationship between golimumab and increased liver enzyme concentrations not clear because many patients received concomitant therapy with drugs that increase liver enzyme concentrations (e.g., methotrexate, NSAIAs).¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in cynomolgus monkeys.¹ Not known whether golimumab is distributed into human milk or absorbed systemically following ingestion.¹ Discontinue nursing or drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Malignancies, some fatal, reported in children and adolescents who received TNF blocking agents.^{1 8} (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Geriatric Use

No overall differences in serious adverse events, serious infections, and adverse events in those ≥65 years of age compared with younger adults.¹ (See Special Populations under Pharmacokinetics.)

Overall incidence of infection is higher in the geriatric population than in younger adults; use with caution.¹

Common Adverse Effects

Upper respiratory infection,¹ nasopharyngitis.¹

Interactions for Golimumab

Administered concomitantly with methotrexate, hydroxychloroquine, sulfasalazine, corticosteroids, and/or NSAIAs in clinical studies.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes.^{1 15}

Drugs metabolized by CYP isoenzymes that have a low therapeutic index: Monitor therapeutic effect and serum concentrations following initiation or discontinuance of golimumab; adjust dosage as needed.^{1 15}

Biologic Antirheumatic Agents

For abatacept, anakinra, rituximab, and other TNF blocking agents, see Specific Drugs under Interactions. Insufficient data available to provide recommendations regarding concomitant use of golimumab and other biologic agents used in the management of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Vaccines

Patients may receive inactivated vaccines.¹

Avoid live vaccines.¹ No data available on response to immunization, risk of infection, or secondary transmission of infection by live vaccines in golimumab-treated patients.¹

Specific Drugs

Drug	Interaction	Comments
Abatacept	Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis1 11	Concomitant use not recommended1 11 15
Anakinra	Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported with anakinra and etanercept (another TNF blocking agent) in rheumatoid arthritis1 10	Concomitant use not recommended1 15
Corticosteroids, oral	Concomitant use does not appear to alter golimumab clearance1
Cyclosporine	Possible effect on cyclosporine metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect and serum concentrations of cyclosporine following initiation or discontinuance of golimumab; adjust dosage as needed1 15
Methotrexate	Concomitant use or nonuse of methotrexate does not appear to influence efficacy or safety of golimumab for management of psoriatic arthritis or ankylosing spondylitis1 Decreased incidence of antibodies to golimumab reported with concomitant use1 Increased mean steady-state trough concentrations of golimumab reported with concomitant use1	Use golimumab in conjunction with methotrexate for management of rheumatoid arthritis1 Golimumab may be used with or without methotrexate for management of psoriatic arthritis or ankylosing spondylitis1
NSAIAs	Concomitant use does not appear to alter golimumab clearance1
Pneumococcal polysaccharide vaccine	Study data suggest that golimumab does not suppress the humoral immune response to pneumococcal vaccine1
Rituximab	Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent1
Sulfasalazine	Concomitant use does not appear to alter golimumab clearance1
Theophylline	Possible effect on theophylline metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect and serum concentrations of theophylline following initiation or discontinuance of golimumab; adjust dosage as needed1 15
TNF blocking agents		Avoid concomitant use of golimumab and other TNF blocking agents1
Warfarin	Possible effect on warfarin metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect of warfarin following initiation or discontinuance of golimumab; adjust dosage as needed1 15

Golimumab Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 53% following sub-Q administration.¹

Peak serum concentrations achieved in a median of 2–6 days following sub-Q administration.¹

Steady-state concentrations achieved within 12 weeks following sub-Q administration of golimumab 50 mg once monthly in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.^{1 18}

Patients who developed antibodies to golimumab generally had lower steady-state trough serum concentrations of golimumab.¹

Distribution

Extent

Distributed mainly into the circulatory system with limited extravascular distribution.¹

Distributed into milk in cynomolgus monkeys; not known whether golimumab is distributed into human milk.¹

Elimination

Half-life

2 weeks in healthy individuals and patients with active rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.¹

Among adults, age does not appear to influence pharmacokinetics.¹ Clearance appears to be similar in patients ≥65 years of age and younger adults.¹ (See Geriatric Use under Cautions.)

With increasing body weight, there is a trend toward higher clearance; however, no clinically important weight-related differences in efficacy observed in psoriatic arthritis or ankylosing spondylitis populations.^{1 18} Reduction in clinical efficacy with increasing body weight observed with both 50- and 100-mg doses in 1 study in rheumatoid arthritis.¹ (See Special Populations under Dosage and Administration.)

No gender-related pharmacokinetic differences apparent in patients with rheumatoid arthritis or psoriatic arthritis; in patients with ankylosing spondylitis, apparent clearance was approximately 13% higher in females than in males.¹ However, both genders achieved clinically important responses at the proposed clinical dose.¹ (See Special Populations under Dosage and Administration.)

Ethnicity-related pharmacokinetic differences not observed between Caucasian and Asian patients; limited number of patients of other races available to assess for pharmacokinetic differences.¹

Stability

Storage

Parenteral

Injection

2–8°C.¹ Protect from light; store in original carton until administration.¹ Do not freeze or shake.¹ Discard unused portions.¹

Actions

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  Potent antagonist of TNF biologic activity.^{1 2 3 4 5 6 14 15 18}

  
  


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  Has high specificity and affinity for soluble and transmembrane TNF (TNF-α); does not bind to or neutralize human lymphotoxin.^{1 3 4 5 6 14 15 18} Prevents the binding of TNF to its receptors, thereby blocking the biologic activity of TNF.^{1 15 18}

  
  


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  Does not appear to bind to other TNF superfamily ligands.¹

  
  


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  Does not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells.¹

  
  


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  An immunoglobulin G₁ kappa (IgG₁) created using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions.¹

  
  


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  Produced by a recombinant cell line cultured by continuous perfusion; purified by a process that includes specific viral inactivation and removal steps.¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  A copy of the manufacturer’s patient information (medication guide) for golimumab must be provided to all patients with each prescription of the drug. (See REMS Program under Dosage and Administration.)^{1 8} Importance of advising patients about potential benefits and risks of golimumab.^{1 8} Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.¹

  
  


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  Importance of instructing patient and/or caregiver regarding proper dosage and administration of golimumab, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.¹

  
  


• 
  

  Risk of increased susceptibility to infection.¹ Importance of promptly informing clinicians if any signs or symptoms of infection (e.g., persistent fever, sweating, cough, dyspnea, fatigue, diarrhea, burning upon urination, warm, red, or painful skin) develop.^{1 9}

  
  


• 
  

  Risk of lymphoma, leukemia, and other malignancies with TNF blocking agents.^{1 8} Importance of informing patients and families about the increased risk of cancer development in children and adolescents, taking into account the clinical utility of TNF blocking agents, the benefits and risks of other immunosuppressive drugs, and the risks associated with untreated disease.⁸ Importance of promptly informing clinicians if signs and symptoms of cancer occur (e.g., unexplained weight loss; fatigue; swollen lymph nodes in the neck, underarm, or groin; easy bruising or bleeding).⁸

  
  


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  Risk of new-onset psoriasis or worsening of existing psoriasis with TNF blocking agents.^{1 8} Importance of informing clinicians of any manifestations of new or worsening psoriasis (e.g., new rash).^{1 8}

  
  


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  Importance of alerting clinician if allergy to latex exists.¹

  
  


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  Importance of informing clinician of any new or worsening medical conditions (e.g., CHF, demyelinating disorders, autoimmune disorders, liver disease, cytopenias, psoriasis).¹

  
  


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  Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.⁸

  
  


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  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of tuberculosis, hepatitis B virus infection, or other chronic or recurring infections.¹

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


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  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Golimumab

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	50 mg/0.5 mL	Simponi (available as disposable prefilled syringes and prefilled auto-injectors [SmartJect])	Centocor Ortho Biotech

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Simponi 50MG/0.5ML Solution (JANSSEN BIOTECH): 1/$1,946.93 or 2/$5,838.00

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Centocor Ortho Biotech Inc. Simponi (golimumab) injection prescribing information. Horsham, PA; 2009 Nov.

2. Smolen JS, Kay J, Doyle MK et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009; 374:210-21. [PubMed 19560810]

3. Keystone EC, Genovese MC, Klareskog L et al. Golimumab, a human antibody to tumour necrosis factor alpha given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009; 68:789-96. [PubMed 19066176]

4. Emery P, Fleischmann RM, Moreland LW et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009; 60:2272-83. [PubMed 19644849]

5. Kavanaugh A, McInnes I, Mease P et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009; 60:976-86. [PubMed 19333944]

6. Inman RD, Davis JC, Heijde D et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008; 58:3402-12. [PubMed 18975305]

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