Golimumab

Dosage Forms & Strengths

SC solution (prefilled syringe/autoinjector)

• Simponi
• 50mg/0.5mL
• 100mg/1mL

IV solution (vial)

• Simponi Aria
• 50mg/4mL

Rheumatoid Arthritis

Indicated for moderately-to-severely active rheumatoid arthritis in combination with methotrexate

Simponi: 50 mg SC qMonth

Simponi Aria: 2 mg/kg IV infused over 30 minutes at weeks 0 and 4, then q8weeks

Psoriatic Arthritis

Indicated alone or in combination with methotrexate for active psoriatic arthritis

50 mg SC qMonth

Ankylosing Spondylitis

Indicated for active ankylosing spondylitis with or without methotrexate

50 mg SC qMonth

Ulcerative Colitis

Indicated for adults with moderate-to-severe ulcerative colitis that is resistant to prior treatment or requires continuous corticosteroid therapy

Initial: 200 mg SC at Week 0, followed by 100 mg SC at Week 2, THEN

Maintenance: 100 mg SC q4weeks

<18 years: Safety and efficacy not established

Polyarticular Juvenile Idiopathic Arthritis (Orphan)

Orphan designation for treatment of polyarticular juvenile idiopathic arthritis in pediatric patients aged ≤16 yr

Sponsor

• Janssen Research & Development, LLC; Welsh & McKean Roads; P. O. Box 776; Spring House, PA 19477

• There are no adequate studies of golimumab in pregnant women.
• It is not known whether this drug is excreted in breast milk.

Golimumab may be found in some form under the following brand names:

• Simponi

• Simponi Aria

Serious side effects have been reported with golimumab including:

Golimumab is a medicine that affects your immune system. Golimumab can lower the ability of your immune system to fight infections. Some people have serious infections while taking golimumab, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that spread throughout their body. Some people have died from these serious infections.

• Your doctor should test you for TB and hepatitis B before starting golimumab.
• Your doctor should monitor you closely for signs and symptoms of TB during treatment with golimumab.

You should not start taking golimumab if you have any kind of infection unless your doctor says it is okay.

Before starting golimumab, tell your doctor if you:

• think you have an infection or have symptoms of an infection such as:
  • fever, sweat, or chills
  • muscle aches
  • cough
  • shortness of breath
  • blood in phlegm
  • weight loss
  • warm, red, or painful skin or sores on your body
  • diarrhea or stomach pain
  • burning when you urinate or urinate more often than normal
  • feel very tired
• are being treated for an infection
• get a lot of infections or have infections that keep coming back
• have diabetes, HIV, or a weak immune system. People with these conditions have a higher chance for infections.
• have TB, or have been in close contact with someone with TB
• live, have lived, or traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis). These infections may happen or become more severe if you use golimumab. Ask your doctor if you do not know if you have lived in an area where these infections are common.
• have or have had hepatitis B
• use the medicine Orencia (abatacept), Kineret (anakinra), Actemra (tocilizumab) or Rituxan (rituximab)

After starting Golimumab, call your doctor right away if you have any symptoms of an infection. Golimumab can make you more likely to get infections or make worse any infection that you have.

Cancer

• For children and adults taking TNF-blocker medicines, including golimumab, the chances of getting cancer may increase.
• There have been cases of unusual cancers in children and teenage patients taking TNF-blocking agents.
• People with inflammatory diseases including rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, especially those with very active disease, may be more likely to get lymphoma.
• Some people treated with golimumab have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with golimumab, tell your doctor.
• Some people receiving medicines that are like golimumab, called TNF-blockers, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF-blocker and another medicine called Imuran (azathioprine) or Purinethol (6-mercaptopurine, 6-MP).

Hepatitis B infection in people who carry the virus in their blood.

If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus can become active while you use golimumab. Your doctor should do blood tests before you start treatment with golimumab and while you are using golimumab. Tell your doctor if you have any of the following symptoms of a possible hepatitis B infection:

• feel very tired
• dark urine
• skin or eyes look yellow
• little or no appetite
• vomiting
• muscle aches
• clay-colored bowel movements
• fevers
• chills
• stomach discomfort
• skin rash

Congestive heart failure (CHF): may worsen current CHF or may cause CHF

• Golimumab should be used with caution in patients with CHF.
• Patients with CHF and also taking golimumab should be closely monitored during therapy.
• Golimumab should be discontinued if new or worsening symptoms of CHF appear.
• Symptoms of CHF include shortness of breath, swelling in arms or legs, and general weakness and fatigue.

New onset or worsening of demyelinating disorders (disorder of the nervous system), including multiple sclerosis or Guillain-Barré syndrome

• Rare cases of this complication have been reported in patients treated with golimumab.
• Discontinuation of golimumab should be considered if this condition occurs.  

Liver Problems

Liver problems can happen in people who use TNF-blocker medicines, including golimumab. These problems can lead to liver failure and death. Call your doctor right away if you have any of these symptoms:

• feel very tired
• skin or eyes look yellow
• poor appetite or vomiting
• pain on the right side of your stomach (abdomen)

Blood Problems

Low blood counts have been seen with TNF-blockers, including golimumab. Your body may not make enough blood cells that help fight infections or help stop bleeding. Symptoms include fever, bruising or bleeding easily, or looking pale. Your doctor will check your blood counts before and during treatment with golimumab.                         

Golimumab may cause dizziness. Do not drive or operate heavy machinery until you know how golimumab affects you.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Golimumab falls into category B. There are no well-controlled studies of golimumab in pregnant women, and so it is unknown whether golimumab can cause fetal harm when administered to a pregnant woman. Golimumab should be used during pregnancy only if clearly needed.

In addition, you should let your baby's doctor know before your baby is given any vaccine. There may be an increased risk of infection with your newborn, particularly within 6 months after birth.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

If you have ever had tuberculosis or hepatitis B, golimumab can cause these conditions to come back or get worse. You should be tested for these conditions before you start using golimumab.

Golimumab is sometimes injected into a vein through an IV. A healthcare provider will give you this type of injection once every 4 to 8 weeks.

Golimumab may also be injected under the skin once every 2 to 4 weeks. You may be shown how to use injections at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles and syringes.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Your care provider will show you the best places on your body to inject golimumab. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Each single-use prefilled syringe or auto-injector device is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Store in the refrigerator, do not freeze. Protect from light. Keep the medication in its original carton until you are ready to give an injection.

Take the prefilled syringe or auto-injector out of the refrigerator and place it at room temperature for 30 minutes before giving your injection. Do not warm the medication with water or heat.

Golimumab can weaken your immune system. Your blood will need to be tested often.

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 24 27 28 29 37 38 39 40 41 42

Psoriatic Arthritis

Used alone or in conjunction with methotrexate for the management of active psoriatic arthritis in adults.1 5 34 35 36

Ankylosing Spondylitis

Used for the management of ankylosing spondylitis in adults with active disease.1 6 32 33

Ulcerative Colitis

Used in adults with moderately to severely active ulcerative colitis who require continuous corticosteroid therapy or who had inadequate response to or were intolerant to conventional therapies (oral aminosalicylates, oral corticosteroids, azathioprine, or mercaptopurine) to induce and maintain clinical response, to improve endoscopic appearance of the mucosa during induction therapy, to induce clinical remission, and to achieve and sustain clinical remission in those who responded to induction therapy.1 26 30

Storage

Parenteral

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

2–8°C.24 Protect from light; store in original carton until administration.24 Do not freeze or shake.24 Discard unused portions.24

Diluted solution: Store up to 4 hours at room temperature.24

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Use golimumab as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• Antipsoriatic Agent
• Antirheumatic, Disease Modifying
• Monoclonal Antibody
• Tumor Necrosis Factor (TNF) Blocking Agent

>10%:

Hematologic & oncologic: Positive ANA titer (≥1:160 titer, newly positive; 17% intravenous, 4% subcutaneous)

Infection: Infection (27% to 28%)

Respiratory: Upper respiratory tract infection (includes laryngitis, nasopharyngitis, pharyngitis, and rhinitis; 13% to 16%)

1% to 10%:

Cardiovascular: Hypertension (3%)

Central nervous system: Dizziness (<1% to 2%), paresthesia (<1% to 2%)

Dermatologic: Skin rash (3%)

Gastrointestinal: Constipation (≤1%)

Hematologic & oncologic: Leukopenia (≤1%)

Hepatic: Increased serum ALT (subcutaneous 4%; ≥3 x ULN: 2%; ≥5 x ULN: <1%), increased serum AST (<1% to 3%)

Immunologic: Antibody development (3% to 7%)

Infection: Viral infection (4% to 5%; includes herpes and influenza), fungal infection (superficial; <1% to 2%), bacterial infection (intravenous 1%), serious infection (≤1%)

Local: Injection site reaction (subcutaneous 3% to 6%)

Respiratory: Bronchitis (2% to 3%)

Miscellaneous: Fever (2%), infusion related reaction (intravenous 1%)

<1% (Limited to important or life-threatening): Anaphylaxis, antibody development (anti-dsDNA), aspergillosis, atypical mycobacterial infection (subcutaneous), blastomycosis, bullous skin disease, candidiasis, cardiac failure (worsening or new onset), cellulitis, coccidioidomycosis, demyelinating disease of the central nervous system, hepatotoxicity (idiosyncratic) (Chalasani 2014), histoplasmosis, Hodgkin lymphoma (initiation of therapy ≤18 years old), hypersensitivity angiitis (subcutaneous), hypersensitivity reaction, infective bursitis (subcutaneous), interstitial pulmonary disease (subcutaneous), leukemia, lupus-like syndrome, malignant lymphoma, malignant melanoma, malignant neoplasm (other than nonmelanoma skin cancer), Merkel cell carcinoma, multiple sclerosis, non-Hodgkin lymphoma (initiation of therapy ≤18 years old), neutropenia, optic neuritis, pancytopenia, peripheral demyelinating polyneuropathy, pneumocystosis, pneumonia, psoriasis (subcutaneous) including new onset, palmoplantar, pustular, or exacerbation), pyelonephritis, reactivation of HBV, sarcoidosis, sepsis, septic arthritis (subcutaneous), septic shock (subcutaneous), serious infection, thrombocytopenia, tuberculosis (including reactivation of latent and new infection), vasculitis (subcutaneous)

Concerns related to adverse effects:

• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.

• Demyelinating disease: Rare cases of new-onset or exacerbation of demyelinating disorders (eg, multiple sclerosis, optic neuritis, Guillain-Barré syndrome, polyneuropathy) have been reported. Consider discontinuing in patients who develop peripheral or CNS demyelinating disorders during treatment. Use with caution in patients with pre-existing or recent onset central or peripheral nervous system demyelinating disorders.

• Heart failure: Worsening and new-onset heart failure (HF) (some fatal) have been reported with golimumab and other TNF-blockers. Monitor closely and discontinue with onset or worsening of symptoms. Use with caution in patients with HF or decreased left ventricular function. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hematologic effects: Cases of pancytopenia and other significant cytopenias, including aplastic anemia, have been reported with TNF-blocking agents. Pancytopenia, leukopenia, neutropenia, and thrombocytopenia have occurred with golimumab. Consider discontinuing with significant hematologic abnormalities. Use with caution in patients with underlying hematologic disorders.

• Hepatitis B: Rare reactivation of hepatitis B virus (HBV), sometimes fatal, has occurred in chronic virus carriers, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Patients who test positive for HBV surface antigen should be referred for hepatitis B evaluation/treatment prior to golimumab initiation. Monitor for clinical and laboratory signs of active infection during and for several months following discontinuation of golimumab treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.

• Hypersensitivity reactions: Severe systemic hypersensitivity reactions (including anaphylaxis) have been reported (some have occurred with the first dose) following intravenous and subcutaneous administration. Symptoms associated with reactions may include dyspnea, hives, nausea, and pruritus; reactions occurred during and within 1 hour of the start of IV infusion. Discontinue immediately if signs develop and initiate appropriate treatment.

• Infections: [US Boxed Warning]: Patients receiving golimumab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids). Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral, or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving TNF-blocking agents, including golimumab. May present as disseminated (rather than local) disease. Histoplasmosis testing (antigen or antibody) may be negative in some patients with active infection. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised (consider risks versus benefits) when considering use in the elderly, patients taking concomitant immunosuppressants, patients with chronic or recurrent infection, patients who have been exposed to tuberculosis, patients with a history of opportunistic infection, patients with comorbid conditions that predispose them to infections (eg, diabetes), or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis). Do not initiate golimumab therapy in patients with active infection, including localized infection, which is clinically important. Patients who develop a new infection while undergoing treatment should be monitored closely.

• Malignancy: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescent patients receiving TNF-blocking agents. Half of the malignancies reported in children were lymphomas (Hodgkin and non-Hodgkin) while other cases varied and included malignancies not typically observed in this population. The onset of malignancy was after a median of 30 months (range: 1 to 84 months) after the initiation of the TNF-blocking agent; most patients were receiving concomitant immunosuppressants. The impact of golimumab on the development and course of malignancy is not fully defined. Compared with the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Lymphomas and other malignancies were also observed (at rates higher than expected for the general population) in adult patients receiving TNF-blocking agents. Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been associated with TNF-blocking agents, primarily reported in adolescent and young adult males with Crohn disease or ulcerative colitis treated with a TNF-blocking agent and concurrent or prior azathioprine or mercaptopurine. Melanoma and Merkel cell carcinoma have been reported in patients receiving TNF-blocking agents including golimumab. Perform periodic skin examinations in all patients during therapy, particularly those at increased risk for skin cancer. Consider risks versus benefits in patients with a known malignancy (other than a successfully treated nonmelanoma skin cancer) and if considering continuing treatment in a patient who develops a malignancy.

• Tuberculosis: [US Boxed Warning]: Tuberculosis (disseminated or extrapulmonary) has been reported in patients receiving golimumab; both reactivation of latent infection and new infections have been reported. Patients should be evaluated for tuberculosis risk factors and latent tuberculosis infection (with a tuberculin skin test) prior to and during therapy. Treatment of latent tuberculosis should be initiated before use. Monitor for development of tuberculosis throughout treatment in patients with initial negative tuberculin skin tests, patients currently receiving treatment for latent tuberculosis, or patients previously treated for tuberculosis; active tuberculosis has developed in this population during treatment with TNF-blocking agents. Use with caution in patients who have resided in regions where tuberculosis is endemic. Consider antituberculosis therapy if an adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis or for patients with risk factors despite negative skin test. Prior to use, consider risks versus benefits in patients who have been exposed to tuberculosis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution; general incidence of infection is higher in elderly patients.

• Pediatric: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescent patients receiving TNF-blocking agents.

Dosage form specific issues:

• Latex: Some dosage forms may contain dry natural rubber (latex).

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Administration formulation/route: The safety and efficacy of switching between the IV and SubQ formulations and routes have not been studied.

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of infection by live vaccines in patients receiving therapy. In clinical trials, humoral response to pneumococcal vaccine was not suppressed in psoriatic arthritis patients receiving golimumab.

Administration advice:
Subcutaneous
-Allow the prefilled syringe or auto-injector to reach room temperature for 30 minutes before subcutaneous injection. Do not warm in any other way.
-The solution should not be used if discolored, cloudy, or if foreign particles are present.
-Discard any remaining product.
-If multiple injections are required, rotate administration sites.
-Avoid injection into areas where the skin is tender, bruised, red, or hard.

Intravenous
-Calculate the dosage and the number of vials needed based on the recommended dosage of 2 mg/kg and the patient's weight.
-Check that the solution in each vial is colorless to light yellow.
-Dilute the solution with 0.9% sodium chloride to a final volume of 100 mL.
-Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter.
-Do not infuse concomitantly in the same intravenous line with other drugs.
-Infuse the solution over 30 minutes.

Storage requirements:
-Store in a refrigerator (2C to 8C)
-Do not freeze
-Protect from light
-Do not shake